Objective To study the effects and the mechanism of Qiwei Granules on the expression of renal function in KK-Ay mice with spontaneous type 2 diabetes. Methods 8-week-old male KK-Ay mice were fed by research forage for 12 weeks to establish model with diabetic nephropathy,the model mice were randomly divided into model group,Valsartan group,Qi-wei Granules group,PERK inhibitor group with 8 mice in each group. 8 C57 BL/6 J mice were set up as the control group. All the mice received daily gavage administration with corresponding medicines. Fasting plasma glucose（FBG）,24 h urinary excretion（UAER）were examined. At age of 20 weeks,bloody urine and kidney tissue were obtained after anaesthetic death to examine the renal function（BUN,SCr）. The pathological morphology of renal tissue were observed by hemmatoxylin eosin（HE）stain,while the protein expressions of GRP78 and PERK were measured by western blot. Results Compared with the model group,albuminuria and renal function were alleviated in Qiwei Granules group（P<0.05）,the protein level of GRP78 and PERK were significantly decreased（P<0.05）. The pathological changes of kidney tissue were obviously improved. Conclusion QWG could reduce albuminuria and improve renal function in KK-Ay mice with spontaneous type 2 diabetes. The protective effect may be associated with inhibition of PERK signaling pathways.