Folium mori, the leaves of Morus alba L., has traditionally been used for the treatment of diabetic hyperglycemia. It has been shown to induce enhanced NOS expression in the hypothalamus of rats with streptozotocin (STZ)-induced diabetes. In the present study, the effect of Folium mori on the expression of nitric oxide synthase (NOS) in the hypothalamus of STZ-induced diabetic rats was investigated via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Enhanced NAPDH-d expression was detected in the paraventricular nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area of the hypothalamus in the STZ-induced diabetes group. Administration of the aqueous extract of Folium mori to rats with STZ-induced diabetes resulted in decreased NADPH-d positivity. These results suggest that Folium mori treatment is effective in curbing the desire for food under diabetic conditions via modulation of NO expression in the hypothalamus.