Diabetes mellitus is a common and serious metabolic disorder in humans. Streptozotocin (STZ)-induced diabetic rats were shown to produce a significant reduction in the number of proliferating cells in the dentate gyrus. In the present study, the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats with STZ-induced diabetes was investigated via immunohistochemistry. Male Sprague-Dawley rats were divided into four groups: the control-rest group, the control-exercise group, the diabetes-rest group, and the diabetes-exercise group. Each of the animals of the diabetes groups was given a single injection of STZ (50 mg/kg) intraperitoneally. All animals were injected with 5-bromo-2'-deoxyuridine (50 mg/kg) for six consecutive days, starting on the second day after STZ injection, and rats of the exercise groups were made to run on treadmill for 30 min each day over the same period. On the eighth day of the experiment, all animals were sacrificed. In the present results, it was shown that cell proliferation in the dentate gyrus is suppressed under diabetic conditions, and that treadmill is effective in enhancing hippocampal granular cell proliferation in rats with STZ-induced diabetes. These results raise the possibility that treadmill exercise is of help in the alleviation of the central neural sequelae of diabetes mellitus.