We report herein that streptozotocin (STZ)-induced diabetes selectively alters the nociceptive threshold with respect to noxious mechanical stimuli. Mice were rendered diabetic by an injection of STZ (200 mg/kg, IV). In the tail-pinch test, the latency of the biting response to forceps was significantly decreased in animals with diabetes of 2 weeks and 8 weeks duration as compared to that in age-matched controls. However, the nociceptive threshold, as determined by the tail-flick test, was not significantly altered. The level of substance P in the spinal cord was significantly increased in mice that has been diabetic for 2 weeks, while, there was a significant decrease, as compared to control levels, in level of substance P in mice diabetic for 8 weeks. However, the level of somatostatin was not significantly altered in mice diabetic for either 2 weeks or 8 weeks. These data suggest that STZ-induced diabetes selectively alters a neuronal system that involves substance P but not somatostatin in the spinal cord.