Aim To access the effects of leflunomide on experimental atherogensis of rabbits. Methods 24 New Zealand White rabbits were devided into three groups, 8 rabbits were selected as normal-diet control group, 8 rabbits as high-diet control, the others as treatment group administered with leflunomide (5 mg/d). Serum lipids, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), atherosclerotic plaque/intima size ratio of aorta and the number of infiltrating macrophage in plaques were detected on the 0, 8 th week. Results Leflunomide had no effect on the lipids compared with control groups, the level of circulating TNF-α, IL-6, plaque/intima size ratio and the number of infiltrating macrophage in the treatment group was lower than that of control groups (all p<0.001). Conclusions LEF could inhibit the inflammation in the lesion of atherosclerosis of rabbits and attenuate atherogensis of rabbits.