James Hamilton, Duke of Châtellerault

Arms of the earl of Arran (left) and his wife Margaret Douglas (right), Kinneil House

In 1532 Lord Arran married Margaret Douglas, who was about ten years older than him. She was a daughter of James Douglas, 3rd Earl of Morton, and Catherine Stewart, herself a natural daughter of James IV.[8] The marriage was arranged by James Hamilton of Finnart. Margaret Douglas was given the house and lands of Kinneil House for her lifetime should her husband die before her. James Hamilton of Finnart paid Morton 4,000 marks as part of the marriage settlement.[9]

James and Margaret had five sons:

1. James (1537–1609), succeeded him as the 3rd Earl of Arran but became insane in 1562[10]
2. Gavin, died young[11]
3. John (1540–1604), became the 1st Marquess of Hamilton[12]
4. David (died 1611)[13][14]
5. Claud (1546–1621), from whom descend the earls, marquesses and dukes of Abercorn[15]

—and four daughters:

1. Barbara, married in 1553 James Fleming, 4th Lord Fleming[16][17]
2. Jean, married Hugh Montgomerie, 3rd Earl of Eglinton in 1555[18][19]
3. Anne (c. 1535 – before April 1574), married George Gordon, 5th Earl of Huntly[20]
4. Margaret, married Sir Alexander Pethein (Peden)[21]

In 1544 Arran tried to divorce his wife. She seemed to have been suffering of poor mental health.[22] Significantly two of their sons, James and Claud, later became insane.

An inventory of a chest of Margaret Douglas's clothes includes a purple velvet night gown with gold passementerie lined with red taffeta, a gown of black cloth of gold with gold passementerie lined with black taffeta, and other gowns and kirtles.[23]

Henry VIII by Hans Holbein the Younger, 1540

Initially, Arran was a Protestant and a member of the pro-English party. In 1543 he helped to negotiate the marriage of the young Queen Mary to Edward, son of King Henry VIII of England, who had broken with Rome. In the same year he authorised the translation and reading of the Bible in the vernacular.[27] On 27 January 1543 he arrested Cardinal Beaton, who favoured the Auld Alliance. Beaton was imprisoned at Dalkeith Palace and then Blackness Castle. However, Henry VIII doubted Arran's commitment to English policy and wanted him deposed. On 18 March 1543, Sir George Douglas of Pittendreich, brother of Lord Angus, told the English ambassador, Ralph Sadler, that:

"if there be any motion now to take the Governor from his state, and to bring the government of this realm to the king of England, I assure you it is impossible to be done at this time. For, there is not so little a boy but that he will hurl stones against it, and the wives will handle their distaffs, and the commons universally will rather die in it, yea, and many noblemen and all the clergy be fully against it."[28]

In September 1543 Arran turned around. He secretly met Cardinal Beaton at Callendar House and reconciled himself with his former enemy. Shortly after he became Catholic and joined the pro-French faction.[29] Around this time Friar Mark Hamilton wrote a history of the Hamilton family.[30][31] A seven-year war with England now called the Rough Wooing followed, which was declared on 20 December 1543, and signed by Arran the following month.[32] The declaration of war was brought by Henry Ray to give to the Parliament of Scotland. Arran replied that the parliament was dissolved, and so he thought it expedient not to answer Henry VIII on the points raised at the time.[33]

In 1544 an attempt was made to transfer the regency from him to Mary of Guise, Queen Mary's mother, but Arran fortified Edinburgh and her forces retired. However, in March 1545 he agreed to abandon some of his responsibilities to her.[34]

In June 1547 Arran gathered a large army to expel the English from Langholm and the surrounding area. He had a banner made from taffeta decorated with gold foil and colours, and another banner for his trumpeter. Horses dragged the artillery and carts laden with cannonballs and tents out of Edinburgh Castle. The guns were dragged toward Langholm with oxen.[35] Arran had an armoured "jack" covered with purple taffeta, then changed his mind, choosing purple velvet.[36] A Scottish spy, David Maitland, who signed himself "Ye Wait Quha" wrote of the preparations to Thomas Wharton, that it was "the starkest host and the monest, and with the best order that wes sen Flodwn", that is, "the strongest host and most numerous, in the best order since Flodden."[37]

A 1558 coin depicting Queen Mary and King Francis

In September 1547 Arran assembled a large Scottish army to resist an English invasion led by Edward Seymour, Duke of Somerset but was defeated at the battle of Pinkie.[38] He was forced to abandon some of his clothes at the battlefield.[39] He nevertheless held onto the regency and continued to lead forces against the occupying troops. For two weeks in February 1548 Arran led a campaign in Teviotdale with Monsieur d'Essé to recapture Ferniehirst Castle and punish borderers. He held discussions at Jedburgh with Nicolas Durand de Villegaignon over the site and financing of a new fort.[40]

Arran reluctantly agreed in July 1548 to Mary's marriage to Francis, eldest son of King Henry II of France. Henry II rewarded him by making him Duke of Châtellerault on 8 February 1549 and a knight of the Order of Saint Michael.[41][38]

On 19 April 1550 Regent Arran and his Privy Council made legislation about foodstuffs and rising prices. The people of Scotland were to reduce their diets and banqueting. Prices were set for wild birds and rabbits, swans would be 5 shillings, plovers 5 pence. River birds including herons and ducks were to be caught by hawking. It was forbidden to shoot deer or birds for the table with "half hag or culverin or pistolate". These acts were ratified by Parliament.[42]