The effects of fruit and vegetable extract (Oxxynea) on plasma cholesterol, early atherosclerosis, cardiac production of superoxide anion, and NAD(P)H oxidase expression were studied in an animal model of atherosclerosis. Thirty six hamsters were divided into two groups of 18 and fed an atherogenic diet for 12 weeks. They received by gavage either water or Oxxynea in water at a human dose equivalent of 10 fruits and vegetables per day. Oxxynea lowered plasma cholesterol and non-HDL cholesterol, but not HDL-cholesterol, and increased plasma antioxidant capacity. It also strongly reduced the area of aortic fatty streak deposition by 77%, cardiac production of superoxide anion by 45%, and p22phox subunit of NAD(P)H oxidase expression by 59%. These findings support the view that chronic consumption of antioxidants supplied by fruits and vegetables has potential beneficial effects with respect to the development of atherosclerosis. The underlying mechanism is related mainly to inhibiting pro-oxidant factors and improving the serum lipid profile.