Anti-atheromatous effects of fenofibrate were studied in KHC rabbits with a hereditary deletion in LDL receptors, a defect similar to that in Watanabe heritable hyperlipidemic rabbits. KHC rabbits (10-weeks-old) were given a dietary admixture of fenofibrate (ca. 30 or ca. 100 mg/kg/day) for 20 weeks. Fenofibrate did not change serum total cholesterol, high density lipoprotein and triglyceride levels. Fenofibrate decreased the percent of plaque area formation in the thoracic aorta, but not the degree of foam cell formation, fibrosis and edematous change, and thickness of the intima. Furthermore, fenofibrate markedly inhibited the medial damage with foam cell formation in the aorta at week 20. From these results, we conclude that fenofibrate manifested the anti-atheromatous effect in KHC rabbit and also the previous model of cholesterol-fed rabbits, particularly against the medial damage in KHC rabbits, independent of the hypolipidemic effect.