During exercise, obese individuals oxidize less glycogen and more fat than their lean counterparts. Since many obese individuals are insulin-resistant, the shift in substrate use may be mediated by insulin resistance rather than body fat. In addition, insulin-resistant individuals with Type-2 diabetes are not resistant to contraction-mediated glucose uptake during exercise, but in vivo studies uncomplicated by hyperglycemia are lacking. The purpose of this study was to compare blood glucose uptake and the balance between carbohydrate and fat utilization during exercise in insulin-resistant (IR) and insulin-sensitive (IS) women while controlling for body fatness, aerobic capacity, and lean body mass. Twelve overweight sedentary women were divided into 2 equal groups based on the Composite Insulin Sensitivity Index (C-ISI). The groups had similar BMI (IR= 28.5±1.6, IS= 27.5±1.9), lean mass (IR= 42.4±1.8 kg, IS= 41.5±1.9 kg) and VO₂max (IR= 29.7±3.5 ml/kg/min, IS= 30.7±3.9) but markedly different C-ISI (IR=3.0±0.7, IS= 7.7±0.9). Blood glucose uptake (Rd), total carbohydrate oxidation (CHO_ox), and estimated muscle glycogen use (EMGU) were assessed using stable isotope dilution and indirect calorimetry during 50' of treadmill walking at 45% VO₂max. CHO_ox and EMGU were significantly lower and total fat oxidation tended to be higher in the IR group. Glucose Rd was nearly identical in the IR and IS groups. These data suggest that insulin resistance, independent of body fat, spares muscle glycogen and shifts substrate oxidation toward greater fat use during exercise. Insulin-resistant individuals with normoglycemia appear to have no defect in blood glucose uptake during exercise.