It has been reported that increased platelet aggregation is associated with the development of diabetic complications. We examined the effect of alterations in diabetic treatment, from diet alone to sulphonylurea (glyburide) and from sulphonylurea to insulin, on platelet aggregation, phos phoinositidemetabolism and protein phosphorylation in patients with NIDDM. Low-dose thrombin-stimulated platelet aggregation and phosphatidic acid (PA) formation were suppressed by the alteration of diet alone to sulphonylurea administration. Moreover, substitution of insulin treatment for sulphonylurea administration resulted in decreased ADP-, collagen- and thrombin stimulatedplatelet aggregation, and thrombin-induced PA formation. In conclusion, both sul phonylureaand insulin treatments suppressed platelet aggregation via suppression of thrombin inducedactivation of phosphoinositide metabolism.