High fat feeding (HFF) is a well-accepted model of nutritionally-induced insulin resistance. This investigation was designed to assess the metabolic responses of female lean Zucker rats provided regular chow (4% fat) or a high fat chow (50% fat) for 15 weeks. HFF rats spontaneously adjusted food intake so that daily caloric intake matched that of chow-fed (CF) controls. HFF animals consumed more (p<0.05) calories from fat (31.9 ± 1.2 kcal/day vs. 2.4 ± 0.2) and had significantly greater final body weights (280 ± 10 g vs. 250 ± 5) and total visceral fat (24 ± 3 g vs. 10 ± 1). Fasting plasma insulin was 2.3-fold elevated in HFF rats. Glucose tolerance (58%) and whole-body insulin sensitivity (75%) were impaired in HFF animals. In HFF plantaris muscle, in vivo IR- and IRS-1 tyrosine phosphorylation and phosphorylation of Akt ser473 and glycogen synthase kinase-3 (GSK-3) ser9, relative to circulating insulin levels, were decreased by 40-59%. In vitro insulin-stimulated glucose transport in HFF soleus was decreased by 54%, as were IRS-1 tyrosine phosphorylation (26%) and phosphorylation of Akt ser473 (38%) and GSK-3 ser9 (25%), the latter indicative of GSK-3 overactivity. GSK-3 inhibition in HFF soleus using CT98014 increased insulin-stimulated glucose transport (28%), IRS-1 tyrosine phosphorylation (28%) and phosphorylation of Akt ser473 (38%) and GSK-3 ser9 (48%). In summary, female lean Zucker rats fed a high-fat diet represent an isocaloric model of nutritionally-induced insulin resistance associated with moderate visceral fat gain, hyperinsulinemia, and impairments of skeletal muscle insulin signaling functionality, including GSK-3 overactivity.