Epidemiological studies have shown that red wine consumption is associated with less cardiovascular mortality in the general population and in the diabetic patients. To determine whether red wine improves insulin resistance in diabetic patients and to explore the relation between insulin sensitivity and endothelial function, we studied vascular reactivity and insulin-mediated glucose uptake in 9 type 2 diabetic patients before and after 2 weeks of red wine consumption (360 mL/d, wine-treated diabetics) and 8 type 2 diabetic patients who did not consume wine (control diabetics). Vascular reactivity was evaluated by plethysmography during intraarterial infusion of acetylcholine (Ach), sodium nitroprusside, and L-N-monomethylarginine. Forearm nitrite balance was measured during Ach infusion. Insulin sensitivity was measured by euglycemic hyperinsulinemic clamp at 1 mU/kg per minute. The basal forearm blood flow and the response to Ach, to sodium nitroprusside, and to L-N -monomethylarginine were unchanged both in the wine-treated and in the control diabetics. In contrast, insulin-mediated whole body glucose disposal improved by 43% after red wine consumption (from 2.79 +/- 0.4 to 4.02 +/- 0.5 mg/kg of lean body mass per minute, P = .02), but did not change in the control group. In conclusion, red wine consumption for 2 weeks markedly attenuates insulin-resistance in type 2 diabetic patients, without affecting vascular reactivity and nitric oxide production.