Objective To observe the effects of astragalus and puerarin injections on the expression of78-k D glucose-regulated protein（ GRP78） in KKAymice with diabetic nephropathy. Methods Male KKAymice were randomly divided into model group and treatment group

and C57 BL /6J mice were used as normal control group. The mice in treatment group were given intraperitoneal astragalus injection and puerarin injection from the 12 th week. The mice were sacrificed in the 16 th week. The blood serum was collected for detecting the levels of fasting blood glucose

urea

creatinine

triglycerides

and total cholesterol. The kidneys were removed and the renal pathological changes were observed. The expression of GRP78 in the renal tissues was examined using immunohistochemical staining. Results Blood biochemical tests in mice showed that

compared with normal mice

the levels of fasting blood glucose

urea

creatinine

total cholesterol and triglycerides increased significantly in model group（ P < 0. 01）.Compared with model group

the levels of fasting blood glucose

urea and the creatinine decreased markedly in treatment group（ P < 0. 05 or P < 0. 01）. Under morphological observation

vacuoles were discovered in the cytoplasm of renal tubular epithelial cells in model group. After treatment

the structure of glomerular and tubular were intact

and there were no apparent pathological changes.Immunohistochemistry showed that the expression of GRP78 protein in treatment group was significantly lower than model group（ P < 0. 01）. Conclusion Astragalus injection and puerarin injection used together can reduce the degree of endoplasmic reticulum stress and protect the function of kidney through inhibiting the expression of GRP78 to certain extent.