High-fat and high-sucrose diets increase the contribution of gluconeogenesis to glucose appearance (glc R_a) under basal conditions. They also reduce insulin suppression of glc R_a and insulin-stimulated muscle glycogen synthesis under euglycemic, hyperinsulinemic conditions. The purpose of the present study was to determine whether these impairments influence liver and muscle glycogen synthesis under hyperglycemic, hyperinsulinemic conditions. Male rats were fed a high-sucrose, high-fat, or low-fat, starch control diet for either 1 (n = 5-7/group) or 5 wk (n = 5-6/group). Studies involved two 90-min periods. During the first, a basal period (BP), [6-³H]glucose was infused. In the second, a hyperglycemic period (HP), [6-³H]glucose, [6-¹⁴C]glucose, and unlabeled glucose were infused. Plasma glucose (BP: 111.2 ± 1.5 mg/dl; HP: 172.3 ± 1.5 mg/dl), insulin (BP: 2.5 ± 0.2 ng/ml; HP: 4.9 ± 0.3 ng/ml), and glucagon (BP: 81.8 ± 1.6 ng/l; HP: 74.0 ± 1.3 ng/l) concentrations were not significantly different among diet groups or with respect to time on diet. There were no significant differences among groups in the glucose infusion rate (mg · kg¹ · min¹) necessary to maintain arterial glucose concentrations at ~170 mg/dl (pooled average: 6.4 ± 0.8 at 1 wk; 6.4 ± 0.7 at 5 wk), percent suppression of glc R_a (44.4 ± 7.8% at 1 wk; 63.2 ± 4.3% at 5 wk), tracer-estimated net liver glycogen synthesis (7.8 ± 1.3 µg · g liver¹ · min¹ at 1 wk; 10.5 ± 2.2 µg · g liver¹ · min¹ at 5 wk), indirect pathway glycogen synthesis (3.7 ± 0.9 µg · g liver¹ · min¹ at 1 wk; 3.4 ± 0.9 µg · g liver¹ · min¹ at 5 wk), or tracer-estimated net muscle glycogenesis (1.0 ± 0.3 µg · g muscle¹ · min¹ at 1 wk; 1.6 ± 0.3 µg · g muscle¹ · min¹ at 5 wk). These data suggest that hyperglycemia compensates for diet-induced insulin resistance in both liver and skeletal muscle.