The effect of a high cholesterol (HQ diet on lipid levels and oxidative stress in the plasma, liver, and aorta was investigated in rabbits and rats. Rabbits were fed a standard diet containing 1% (w/w) pure cholesterol for 2 months. Rats were fed a diet consisting of the standard diet supplemented with 2% (w/w) pure cholesterol and 0.5% (w/w) cholic acid for 4 months. The HC diet caused significant increases in cholesterol and lipid peroxide levels in plasma and aorta in rabbits. However, plasma cholesterol levels increased only slightly in rats on a HC diet, and there was no effect on aortic cholesterol and lipid peroxide levels. However, the HC diet altered lipid levels and lipid peroxidation as well as glutathione levels and antioxidant enzyme activities in the livers of rabbits and rats in a similar way. Thus, oxidative changes in the plasma and aorta may play an additive role in the formation of atheroma plaques in rabbits after the HC diet. (C) 2004 Elsevier Inc. All rights reserved.