Increased levels of serum cholesterol (CHO) are associated with a risk of coronary artery disease. The beneficial effect of various dietary components on hypercholesterolemia and atherosclerosis was reviewed based on our animal experiments. Exogenously hypercholesterolemic (ExHC) rats, a strain susceptible to dietary CHO, show increased secretion of β-very-low-density lipoproteins (VLDL) and reduced uptake of lipoproteins by the liver. Exposure of ExHC rats to a high-cholesterol diet in early life exerted a long-lasting effect leading to transient suppression of hypercholesterolemia in later life. Dietary polyunsaturated fats, particularly those containing docosahexaenoic acid (DHA), were effective in lowering serum lipid levels in comparison with saturated fats, but stearic acid-containing fats were less hypercholesterolemic because they interrupted the intestinal absorption of CHO. The hypocholesterolemic action of dietary phosphatidylethanolamine was attributed to the ethanolamine constituent, which prevented methylation of the phospholipid to phosphatidylcholine in primary cultured hepatocytes, consequently leading to suppression of VLDL-CHO secretion. Soybean protein and DHA were found to be beneficial for reducing atherosclerosis in both ExHC rats and apo E-deficient mice.