Exercise-induced hyperketonemia was investigated using streptozotocin (STZ)-diabetic rats subjected to running exercise on a treadmill. The degrees of hyperketonemia after 50, 55 and 60% VO2max of exercises were similar in mild diabetic rats (fasting plasma glucose; FPG less than 11 mM). The degree of hyperketonemia (especially an increase in acetoacetate; AcAc) after 60% VO2max of exercise was correlated with FPG (P less than 0.01) and basal plasma ketone bodies (P less than 0.01). Prolonged training with 60% VO2max of exercise for 30 min 3 times per week for 6 wks reduced the increase in plasma ketone bodies induced by the exercise in both mild (FPG less than 11 mM) and severe (FPG greater than 22 mM) diabetic rats. The exercise-induced increase in plasma glucagon in mild diabetic rats and free fatty acids (FFA) in severe diabetic rats are also reduced by the training. These results demonstrate that exercise-induced hyper-AcAc-emia correlated with the FPG level is reduced by prolonged training in diabetic rats, and might suggest that exercise-induced hyperketonemia is reduced by long-term exercise training also in diabetic patients.