Abstract: OBJECTIVE To elucidate the protective effect of Erzhi formula (EZF) on the podocyte injury in diabetic nephropathy (DN) rats. METHODS STZ and high glucose and high-fat diet were used to replicate the diabetic nephropathy rat model. The changes of blood glucose， urine protein， renal index， renal pathological changes (HE/PAS staining)， and CD2AP and podocin protein expression in the podocyte membranes were investigated. RESULTS After 8 weeks treatment of EZF extraction， each dose group showed hypoglycemic effect. Compared with the model group， EZF extraction significantly decreased the 24 h urinary protein (P<0.05); After 16 weeks intervention， the body weight in the model rats were significantly reduced (P<0.01)， renal index were increased significantly (P<0.05); HE and PAS staining showed that the pathological changes of model rats were alleviated and the glomerular morphology were normal after the treatment of EZF extraction. The expression of CD2AP and Podocin protein in DN rat kidney were detected by Western blotting method. The results showed that compared with the model group， EZF significantly increased the expression podocin and CD2AP protein (P<0.05，P<0.01). CONCLUSION EZF can inhibit renal injury and repair renal function in diabetic rats， and this function may be mediated by the protection of the podocyte and the regulation of the expression of CD2AP and podocin in its pore membrane protein.