Opiates, chiefly morphine, are commonly known as the best drugs for relief of pain, but due to development of tolerance and the physical or mental dependency the use of these drugs are restricted. Several neuroendocrine complications including diabetes change the antinociception of morphine and the development of tolerance and dependency to this drug. The withdrawal signs in diabetic rats significantly reduce in comparing to non-diabetic animals. The exact mechanism of these effects has not been known yet. Due to known role of nitric oxide in development of morphine tolerance this study was designed to evaluate the role of nitric oxide in the effects of diabetes on morphine tolerance. In this study the alloxan-induced diabetic male rats are used, and the changes in nitric oxide level is measured by spectrophotometric method. These changes are also measured in tolerant animals after the injection of repeated doses of morphine sulfate and by the use of inhibitors or producers of NO syntheses we are trying to clarify the role of this neurotransmitter in diabetic state.