The Nisqually River is the traditional territorial center of the Nisqually tribe, for which it was named, though they also lived throughout southern Puget Sound. The Treaty of Medicine Creek, one of the major Northwest treaties between Washington territory and the native population of Puget Sound, was signed near a creek at the site of what is now a wildlife refuge near the delta of the river. The Nisqually were moved from the river and much of the surrounding region after the signing of the treaty, settling on a reservation on Puget Sound east of Olympia. After a period of resistance by the Nisqually tribe, including such leaders as Chief Leschi, a new reservation three times the size of the original was established on the river.