Objective: To investigate the effect of bufalin against proteinuria in adriamycin (ADR)-induced nephritic rats and its possible mechanisms. Methods: Forty SD rats were randomly divided into three groups: control group,model group and bufalin group. At the beginning,7.5 mg/kg ADR was singly administered through the tail vein except for the control rats. After 7 days,the rats in bufalin group were injected intraperitoneally with 0.1 mg/kg bufalin everyday unitl day 28. Total 24-h urine samples of all groups were collected weekly. At the end,biological parameters and oxidative stress in blood serum were measured,the histopathology of the renal cortex were detected by light microscopy and transmission electron microscopy,the expression of integrin-linked kinase(ILK) was qualified by Western blot. Results: Bufalin could reduce the 24-h urinary protein and blood lipid,alleviate the podocyte damage,inhibit the oxidative stress and down-regulate ILK in the protein level in ADR rats. Conclusion: Bufalin may against proteinuria by protecting podocyte,and its possible mechanisms against podocyte damage are related to inhibit the oxidative stress and down-regulate ILK in the protein level.