Diabetes mellitus is a metabolic disorder with serious sequelae in humans. Hyperphagia is a characteristic symptom of diabetes and is a central nervous system-mediated disorder. Neuropeptide Y (NPY) is a 36-amino-acid peptide and is concentrated in the hypothalamus which is an appetite-regulating area. NPY is known to stimulate appetite and decrease energy expenditure. In the present study, the effect of treadmill exercise on the hypothalamic NPY expression in rats with streptozotocin (STZ)-induced diabetes was investigated via immunohistochemistry. Enhanced NPY expression in the paraventricular nucleus and arcuate nucleus was observed in the STZ-induced diabetic rats. Treadmill exercise suppressed a diabetes-induced increase of NPY expression. The present results suggest the possibility that treadmill exercise inhibits diabetes-induced increment of the desire for food.