In the present study, the effect of acupuncture at Zusanli acupoint on nitric oxide synthase (NOS) expression in the hippocampus of streptozotocin (STZ)-induced diabetic rats was investigated via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Animals were divided into four groups: the control group, the nondiabetic and acupunctured group, the STZ-induced diabetes group, and the STZ-induced diabetes and acupunctured group. From the results, NADPH-d-positive neurons in the hippocampus were decreased in STZ-induced diabetic rats, while acupuncture increased NOS expression significantly under diabetic conditions. In the present study, it can be suggested that acupuncture treatment may modulate NOS activity in the hippocampus under diabetic conditions.