Although insulin resistance has been involved in the pathogenesis of essential hypertension in non-diabetic patients, few studies were performed regarding to the association between insulin resistance, hypertension and nephropathy in diabetes mellitus. We observed the changes of blood pressure and proteinuria for 7 years in normotensive 28 patients with non-insulin-dependent diabetes mellitus (NIDDM), following measurement of insulin sensitivity. Patients were over 40 years old and not obese, and fasting plasma glucose levels were less than 140 mg/dl. Insulin sensitivity was determined using glucose-clamp method or glucose, insulin, and somatostatin infusion method. In 28 subjects, 12 subjects developed hypertension and 16 subjects were remained normotensive. Insulin induced glucose clearance was significantly decreased in subjects developed hypertension (30 +/- 12 ml/kg/10 min) than in subjects remained normotensive (50 +/- 19 ml/kg/10 min). Furthermore, we found significantly higher incidence of proteinuria in patients developed hypertensive (7 out of 12 patient) than in patients remained normotensive (one out of 16 patients; p < 0.05). These results suggest that insulin resistance is involved in the etiology of hypertension in NIDDM patients, and that this derangement has an important role for the progression of diabetic nephropathy.