Abstract: Objective To investigate the expression of osteopontin (OPN) and monocyte chemoattractant protein 1(MCP-1)and the effect of simvastatin on them in diet-hypercholesterolemia rats. Methods Wistar rats were divided into three groups: control rats, cholesterol fed rats and cholesterol fed rats treated with simvastatin (10 mg ? kg-1? d -1). Twelve weeks later, we measured the 24 hours total urine protein, creatinine clearance , total serum cholesterol, LDL cholesterol.HDL cholesterol and triglycerides. kidney pathology was observed. Immunohistochemistry was used to analyse the expression of MCP -1. The expression of OPN in kidney tissue were detected by RT-PCR and western blot. Results As compared to control group rats ,the total serum cholesterol, LDL—cholesterol level, triglycerides and 24 h total urine protein increased in hypercholesterolemia group rats（P＜0.01) . but it decreased significantly in simvastatin treated group compared with hypercholesterolemia group（P<0.01）. the renal pathological lesion was ameliorated in simvastatin treated group; As compared to control group rats ,the expression of MCP-1 increased in cortical tubular epithelium and the expression of OPN increased in hyperlipemia group, and the expression of MCP-1 and OPN was significantly decreased in the simvastatin treated groups after 12 weeks（P<0.05）. Either the expression of MCP-1 or urine protein was positively correlated with the expression of OPN in renal tissues.Conclusion The expression of OPN and MCP-1 were increased and had a close relationship with macrophage infiltration into tubulointerstitium in Hypercholesterolemia rats．Simvastatin has some protective effect partly through down regulating OPN and MCP-1 expression and reducing macrophage infiltration．