It has been reported that insulin treatment improves hypertension in the patients with diabetes mellitus. The mechanisms of the antihypertensive effect of insulin, however, remains to be fully elucidated. Nitric oxide (NO) is generated in the endothelial cells and tonically regulates blood pressure. In the present study, we investigated the effect of insulin on NO production in cultured human endothelial cells. Insulin (1μM, 10μM and lOOμM) increased NO metabolite (N02-) levels in the medium and NO synthase (NOS) activity in cultured human endothelial cells. Insulin also stimulated proliferation and mitogen-associated protein kinase activity of the endothelial cells. These findings suggest that insulin reduces blood pressure by stimulating NO production in the endothelial cells, possibly via induction of NOS molecule and proliferation of endothelial cells.