Objective: To investigate the effect of high-cholesterol diet on renal artery atherosclerosis and the amelioration of berberine. Methods: Thirty SPF male Wistar rats were randomly divided into control group (n = 10),experimental group(n = 10) and berberine group(n = 10). Rats of control group were fed with normal diets while the other two groups were fed with high cholesterol diet starting from the second week for 3 months,after which the berberine group were administrated berberine(100 mg/kg) through intragastric administration daily,and the rats from experimental group were given normal saline for totally 6 weeks. Lidocaine was used for anesthesia and blood biochemical parameters such as cholesterol and creatinine were checked. Hematoxylin and Eosin (HE) staining and immunohistochemistry were used to investigate the effect of berberine on the AS lesion of renal artery. RT-PCR and Western blotting was used to study the expression of the IL-18 mRNA and protein. Results: Some of the blood biochemistry parameters of experimental group were significantly different from the other two groups (P < 0.01). The rats of experimental group have generated a significant accumulation of the foam cells and migration of the smooth muscle cells compared with that of the control group,while rats treated with the berberine showed less accumulation of the foam cells and no significant migration of the smooth muscle cells. The relative expression of the IL-18 mRNA increased significantly after induction of renal artery AS compared with that of the control group and the berberine group(both P < 0.01). Conclusion: Berberine can suppress the expression of IL-18 and prevent the formation and development of the AS,consequently protect the renal artery,renal artery stenosis and the damage from renal artery stenosis.