It has known that acupuncture exerts various effects, such as analgesia, promotion of homeostasis, improvements in brain circulation, and rectification of internal disorders in Oriental medicine. Of particular, acupuncture at the Zusanli acupoint (ST36) has been widely used to relieve symptoms of diabetes mellitus. The effect of acupuncture at Zusanli on nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons in streptozotocin (STZ)-induced diabetic rats was investigated via immunohistochemistry. Decreased NADPH-d-positive neurons was detected in cerebrocortex of STZ-induced diabetic rats. Needling on the Zusanli in diabetic rats resulted in increase of NADPH-d-positive neurons in cerebrocortex. The present study indicate that acupuncture may affect NADPH-d-positive neurons in cerebrocortex of STZ-induced diabetic rats.