Abstract: Objective To explore the combined detection of urine UmAlb and urinary nephrin (Unephrin), podocalyxin (UPCX) in podocyte of MKR mice with diabetic nephropathy．Methods Thirty 8 weeks old MKR mice were randomly divided into two groups as follows: negative control group, DN model group, and another 15 wild C57 mice were used as normal control. Mice in DN model group were received unilateral nephrectomy and high-fat diet feed for 2 months. The morphological structure changes of the podocytes were observed by transmission electron microscopes. The levels of FBG were detected by electrochemical detection method, The nephrin and PCX protein expression were measured by western blotting. The levels of UmAlb, Unephrin and UPCX were detected by ELISA. Results The podocyte damage in the mice of DN model group increased significantly when compared with normal control. As compared with normal control, FBG in the model group increased significantly ( P<0.01), the expression level of nephrin and PCX in Renal Tissue and Unephrin, UPCX, and urine UmAlb were also increased significantly ( P<0.01). Conclusion The level of Unephrin and UPCX were positive correlated with the level of urine UmAlb, the loss of podocyte strcture protein might be one of the mechanism in leading proteinuria in diabetic nephropathy.