Abstract: Objective： To establish Chronic Renal Failure （CRF） with high-grade proteinuria rat model. Methods： The 5/6 nephrectomy rat was replicated and fed with high-protein diet. Results： Volume of Scr and 24h proteinuria in CRF rat’s with 40% high-protein diet group were increased significantly than those of normal diet control and 20% high-protein diet group. Renal pathology showed more severely neprosclerosis and matrix fibrosis in 40% high-protein diet group than other groups. Conclusion：CRF with high-grade proteinuria rat models can be established by supplying high-protein diet to replicated 5/6 nephrectomy rats.