Aim To explore the cardioprotection mechanism of red wine and resveratrol, the effects of red wine and resveratrol on platelet aggregation both in vitro and in vivo were studied. Methods Hypercholesterolemia in rabbits was induced by high cholesterol diet. Platelet aggregation induced by thrombin, ADP and collagen was measured by using Born's method. Results Hypercholesterolemia induced by high cholesterol diet enhanced the platelet aggregation in rabbits. Red wine, de alcohol red wine or resveratrol were administered orally, which significantly inhibited ADP induced platelet aggregation in rabbits with hypercholesterolemia. In vitro resveratrol significantly inhibited healthy volunteers' platelet aggregation induced by thrombin, ADP or collagen in a concentration dependent manner. Conclusions Red wine and resveratrol can inhibit platelet aggregation both in vitro and in vivo. This may be one of the mechanisms by which resveratrol prevents against atherosclerosis.