Hypercholesterolemia is a major contributory factor in coronary atherosclerosis. Reactive oxygen metabolites (ROM) have been implicated in the development of hypercholesterolemic atherosclerosis. If ROM are involved in hypercholesterolemic atherosclerosis then garlic which has been shown to have antioxidant activity should be able to protect against it. It is possible that the activity of antioxidant enzymes is altered during hypercholesterolemia.Objectives To investigate the effect of hypercholesterolemic atherosclerosis on the activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] in the blood of rabbits in the absence or presence of garlic.Methods The rabbits were divided into 4 groups; group I control; group II, garlic (600 mg daily); group III, 1% cholesterol and group IV, 1% cholesterol plus garlic. Blood was collected at the beginning and at 4 and 10 weeks for the measurement of activity of antioxidant enzymes.Results There was an increase in the activity of SOD in group III and IV as compared to group I and II at 4 weeks and in group III and IV as compared to group II at 10 weeks. The activity of CAT also increased in group III and IV as compared to group II at 4 and 10 weeks. However, the activity of GSH-Px decreased in group III and IV as compared to group I and II at 4th week while it increased in group IV as compared to group I at 10th week.Conclusion These results suggest that oxidative stress does occur during hypercholesterolemic atherosclerosis and garlic may provide protection by augmenting the activity of antioxidant enzymes.