The effects of exercise training on glucose-stimulated insulin secretion (GSIS) were studied in male Sprague-Dawley rats made mildly to severely diabetic by partial pancreatectomy. Exercise trained (10 wk treadmill; T) and untrained (Unt) rats were grouped according to posttraining fed-state hyperglycemia as follows: T < 200 and Unt < 200 (glucose concn < 200 mg/dl), T 200-300 and Unt 200-300 (glucose concn 200-300 mg/dl), and T > 300 and Unt > 300 (glucose concn > 300 mg/dl). After exercise training, hyperglycemic glucose clamps were performed in awake rats by elevation of arterial blood glucose concentration 126 mg/dl above fasting basal levels for 90 min. Exercise training significantly increased muscle citrate synthase activity. Prevailing hyperglycemia was reduced during the 10-wk exercise training period in all T rats with fed-state glucose concentrations < 300, and only 53% of Unt rats in these groups had reduced glycemia. GSIS was significantly higher in T < 200 [2.4 +/- 0.7 (SD) ng/ml at 90 min] than in Unt < 200 (1.5 +/- 0.3). A similar response was found for T 200-300 (1.1 +/- 0.3 ng/dl) vs. Unt 200-300 (0.7 +/- 0.1) but not T > 300 (0.36 +/- 0.2) vs. Unt > 300 (0.44 +/- 0.05). Sham-operated control rats had insulin concentrations of 6.6 +/- 1.6 ng/ml at the 90th min of the clamp. Acute exercise reduced fed-state glycemia in rats with mild-to-moderate (< 300 mg/dl) diabetes. Because rats were matched for prevailing hyperglycemia during the time of the GSIS determination, it is suggested that, in addition to acute reductions in glycemia due to exercise, other exercise-training-associated mechanisms seem to account for the positive adaptation in these beta-cell-deficient rats.