The Flight of the Earls in 1607 left him as one of the most senior Gaelic figures remaining in Ulster. In 1608 when Sir Cahir O'Doherty launched O'Doherty's Rebellion by burning Derry, MacDonnell did not consider joining forces with him. O'Doherty, a former loyalist to the Crown had been angered at his treatment by local officials. O'Doherty was defeated and killed at the Battle of Kilmacrennan and the rebellion collapsed. In the wake of the rebellion the government decided to bring in a more wide-ranging Plantation of Ulster than had originally been planned. This didn't greatly affect MacDonnell as Counties Antrim and Down were excluded from the Plantation, as large-scale Scottish settling was already taking place there.