Purpose: Nitric oxide (NO) plays an important role in homeostatic vasodilation and the regulation of blood flow. On the other hand, excess release of NO causes various vascular complications. There are only a few reports on the relationship between plasma NO levels and microvascular complications, especially diabetic retinopathy (DR) in patients with type 2 diabetes. The purpose of this study was to determine the relationship between plasma NO levels and DR. Methods: In a prospective study, blood samples were obtained from 36 patients with diabetes and no diabetic retinopathy (NDR), 43 patients with nonproliferative diabetic retinopathy (NPDR), 18 patients with proliferative diabetic retinopathy (PDR), and 40 subjects without diabetes mellitus, who served as controls. The levels of plasma NOx (nitrite and nitrate), the stable metabolites of NOx were measured by high-performance liquid chromatography with the Griess method. Results: The plasma NOx levels were 92.8 +/- 16.0, 70.2 +/- 6.8, 90.3 +/- 9.1, and 53.8 +/- 6.1 mu mol/l in patients with NDR, NPDR, or PDR, and in the controls, respectively. The plasma NO, levels in the three diabetic groups were significantly higher than those in the control group (P < 0.05 in each case). Conclusion: The increased plasma NO levels in patients with type 2 diabetes indicate that NO may be associated with the pathogenesis of DR.