The endothelium is the inner lining of our blood vessels and normal functions of endothelial cells include enabling coagulation, platelet adhesion and immune function. Endothelial dysfunction is associated with reduced anticoagulant properties and the inability of arteries and arterioles to dilate fully. The gradual decrease in endothelial function over time is a key factor in the development of diseases associated with ageing, especially cardiovascular disease (CVD). Many epidemiologic studies suggest protection against CVD from moderate intake of alcoholic beverages, especially those rich in antioxidants, such as red wine, which is high in polyphenols (RWPs). This study examined whether intake of red wine polyphenols (RWPs), a rich source of natural antioxidants, prevents ageing-related impairment of vascular function and physical exercise capacity. Vascular reactivity from 12, 20 and 40 week-old rats was assessed in organ chambers. Rats received from week 16 to 40 either solvent, RWPs or the antioxidant and NADPH oxidase inhibitor, apocynin. RWPs and apocynin improved the endothelial dysfunction, normalized oxidative stress and the expression of the different proteins. RWPs also improved ageing-related decline in physical exercise. Thus, intake of RWPs protects against ageing-induced endothelial dysfunction and decline in physical performance.