The lipid-lowering effect of pravastatin on glomerulosclerosis was observed in nephrotic syndrome model, which was induced in rats by using repeated puromycin injections. The histologic changes of the model were similar to those of human focal segmental glomerulosclerosis. Rats were divided into three groups, namely, normal control, nephropathy and nephropathy with pravastatin. Pravastatin was administered through gastric tube 6mg.kg-1.d-1 for 12 weeks. The lipoprotein profile and histologic development were observed. The results showed that pravastatin-treated rats had significantly lower cholesterol, triglycerides, very low density lipoprotein and high density lipoprotein than the nephropathy group at 7 weeks (P < 0.05). Moreover, the renal damage was also less marked in pravastatin-treated rats. Light microscopic and immunohistochemical examination revealed that lipid-lowering therapy was associated with significant lower level of glomerular sclerosing index and less accumulation of extracellular matrix including collagen III, IV, laminine and fibronectin as compared with the nephropathy group. However urinary protein and serum albumin levels were similar in both groups. It is suggested that lipid-lowering thyrapy may retard the progression of glomerulosclerosis and thus preserve renal function. The results imply that hyperlipoidemia plays an important role in the pathophysiological progression of renal disease.