Aim To observe the anti-atheromatous effects of fenofibrate in cholesterol-fed rabbits. Methods 10 male New Zealand white rabbits were fed with high cholesterol diet for 8 weeks,and then were randomly divided into two groups: high cholesterol group maintained cholesterol diet for 4 weeks;fenofibrate treatment group maintained the same cholesterol diet besides supplementing with fenofibrate30 mg/(kg·d)] for 4 weeks.And control group was fed with normal diet for 12 weeks.Before and after feeding,serum tumor necrosis factor-α(TNFα) levels of all rabbits were measured.After feeding,the aortas were harvested for observing the formation of atherosclerotic plaques.TNF-α mRNA expression in adipose tissue was evaluated by reverse transcription-polymerase chain reaction(RT-PCR). Results High cholesterol group and fenofibrate treatment group showed higher serum levels of total cholesterol and low density lipoprotein cholesterol than those of control group(p<0.001),but there were no difference between the two groups(p<0.05).As compared with the high cholesterol group,aortic atherosclerotic area(52.8%±6.9% vs 76.3%±8.6%,p<0.01),intimal thickness of the aorta(28.45±5.68 μm vs 76.18±11.25 μm,p<0.05),serum TNF-α levels(2.11±0.26 ng/L vs 3.86±0.33 ng/L,p<0.05) and TNF-α mRNA expression in adipose tissue (0.31±0.05 vs 0.56±0.07,p<0.05) were significantly decreased in fenofibrate treatment group. Conclusions The study indicates that fenofibrate manifests an anti-atheromatous effect independent of the hypolipidemic effect in cholesterol-fed rabbits and decreasing serum TNF-α level may be one of its possible mechanisms.