This study aims to evaluate the possible protective effects of fish oil, olive oil and melatonin on the induced hypercholesterolemia in adult male rats. 50 rats were used in this study and were divided into 5 groups 10 rats each. Rats of group 1 were fed on a standard diet and those of group 2 were fed on a standard diet enriched with 1% cholesterol (cholesterol fed group). Groups 3-5 were fed as in group 2 and treated at the same time with fish oil in group 3 (fish oil group), with olive oil in group 4 (olive oil group) and with melatonin in group 5 (melatonin group). Blood samples were taken from all animals at the end of the experiment after 10 weeks. The aorta of all animals were obtained after slaughtering and examined histologically to assess the presence of atherosclerosis. Parameters of the lipogram (total plasma cholesterol (TPC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides (TG)], superoxide dismutase (SOD), total thiol, nitric oxide (NO) and lipid peroxide (LP) were measured. Feeding cholesterol significantly increased TPC, LDL, TG and LP and significantly decreased HDL, SOD, NO and total thiol. There was a significant decrease in TPC, LDL, TG and LP by using fish oil, olive oil and melatonin while, the level of SOD, NO and total thiol were significantly increased and non significant increase in the level of HDL. Histological examination of the aorta from rats of the fish oil and olive oil groups showed fatty streaks, which are early atheromatous lesions, compared with typical atherosclerotic fibrous plaques in cholesterol fed group. In melatonin group very early atheromatous lesions were found and they were less pronounced than in fish oil and olive oil group. It was concluded that hypercholesterolemia leads to an increase in TG, LDL, LP and oxidative stress and a decrease in HDL and a depletion of antioxidant enzymes. Fish oil caused the greatest reduction in TG and the greatest increase in NO. Olive oil was the most effective in increasing total thiol and in reducing LP, and melatonin was the best factor reducing TPC, LDL and consequently atherogenesis. Therefore, fish oil, olive oil and melatonin supplementation is recommended to prevent arteriosclerosis that leads to heart attacks, strokes and other forms of cardiovascular damage.