The free radical nitric oxide (NO), generated by inducible form of nitric oxide synthase (iNOS), is a potential mediator of cytokine-induced beta-cell dysfunction. Macrophage derived interleukin-1 beta (IL-1) is important in eliciting beta-cell dysfunction and initiating beta-cell damage in response to microenviromental changes within islets. Destruction of pancreatic islet cells seems to be responsible from increased production of NO by activated macrophages. IL-1, tumor necrosis factor-alpha (TNF-), and interferon-gamma (IFN-) are required for iNOS expression in human islet cells. The purpose of this study was to investigate the relationship between NO and diabetes mellitus by means of determining the serum levels and stable end-products of NO in various clinical patterns of diabetes mellitus in comparison with serum IL-1 levels in 85 diabetic patients and 23 healthy controls. The diabetics had significantly higher serum NO concentrations when compared with healthy controls (p<0.05). Diabetics with or without complications of diabetes had significantly higher NO levels when compared with healthy controls. No difference was noted in serum NO levels according to the type of diabetes and the presence of complications. Serum IL-1 concentration was not detectable in 92% of diabetic patients and of all the healthy controls. As a result, although NO and IL-1 work in synergy, it seems that it is hard to evaluate their role in diabetic patients by means of serum levels only.