Abstract: Objective To explore the role and mechanism of podocytes in rat model with uric acid-induce renal damage.Methods By using a random number table,a total of 24 male Sprague-Dawley rats were randomly divided into three groups of control(NC),model(HUA) and febuxostat(FX) (n=8 each).After 8 weeks,the rats were weighted and sacrificed.The levels of uric acid(UA),blood urea nitrogen(BUN),serum creatinine(Scr) and 24 h urinary protein(24 h UP) were recorded.Renal pathological changes were observed under transmission electron microscope(TEM) after hematoxylin-eosin(HE) staining.The renal expression levels of nephrin and desmin were detected by immunohistochemical staining and Western blot.Results At Week 8,the levels of UA,Scr,BUN,24 h UP and the expression level of desmin increased markedly in HUA group than those in NC group(P<0.01);The expression of nephrin decreased obviously in HUA group.Compared with HUA group,the levels of UA,Scr,BUN,24 h UP and the expression level of desmin decreased obviously in FX group.Massive urate crystals deposited in renal tubules and foot process effacement in HUA group.However,it was lighter in FX group.Conclusion Hyperuricemia causes renal podocyte damage and impairs renal function.Febuxostat treatment can effectively lesson the degree of podocyte damage in hyperuricemia rats.A positive correlation exists between serum uric acid level and desmin expression in renal tissue(P<0.01);a negative correlation between serum level of uric acid and nephrin expression in renal tissue(P<0.01).A linear correlation exists between the level of uric acid and the degree of podocyte injury.Podocyte injury may be one of the causes of uric acid nephropathy.