AIM: To explore the prevention of atherosclerosis by PPARy agonist rosiglitazone. METHODS: 24 male New Zealand white rabbits weighing 1.8 to 2.2 kg were randomly divided into 3 groups: control group, normal rabbit chow; cholesterol group, 1% cholesterol diet; rosiglitazone group, 1% cholesterol diet supplemented with rosiglitazone 0.5 mg x kg(-1) x d(-1) for 6 weeks. Rabbits in cholesterol group and rosiglitazone group were sequentially fed 1% cholesterol-containing diet for 16 weeks. At the end of the experiment, blood glucose, serum lipids levels, ratio of plaque area to aorta area and ratio of intima to media were determined. RESULTS: Hypercholesterolemia was successfully reproduced in rabbits. Adnimistration of rosiglitazone significantly decreased serum TC and LDL-C. The ratio of intima to media and ratio of plaque area to aorta area were also reduced. CONCLUSION: Rosiglitazone could prevent atherosclerosis by decreasing levels of TC and LDL-C.