Elevated plasma free fatty acids (FFA) cause insulin resistance, and are thought to play a key role in mediating insulin resistance in patients with the metabolic syndrome (MTS) and type 2 diabetes (type 2DM). Two experimental models used to study the mechanisms responsible for insulin resistance in patients are high fat diet fed rodents and administration of triglycerides (TG) plus heparin to raise plasma FFA. As evidence that insulin resistance in high fat diet fed rats is due to high FFA, it has been reported that the insulin resistance is rapidly reversed by an overnight fast, a high glucose meal, and an exercise bout. If true, these findings would invalidate the high fat diet fed rodent as a model for the MTS or type 2DM, because insulin resistance is not rapidly reversed by these treatments in patients. The purpose of this study was to determine if diet-induced insulin resistance is, in fact, rapidly reversible. Incubation of muscles in vitro rapidly reversed TG plus heparin, but not high fat diet, induced insulin resistance. Both an overnight fast and a high glucose meal were followed by a large increase in insulin-stimulated muscle glucose transport. However, these are adaptive responses, not reversals of insulin resistance, because they also occurred in muscles of insulin sensitive, chow-fed control rats. Our results show that high FFA, i.e. Randle glucose-fatty acid cycle, induced insulin resistance is transient. In contrast, the insulin resistance induced by a high fat diet does not reverse rapidly.