Twelve of the 48 male SD rats were randomly selected as normal control group （n=12）， and the remaining 36 rats were intraperitoneally injected with streptozotocin （STZ） to establish the diabetes models， and then randomly divided into model group （n=12）， liraglutide group（n=12） and liraglutide+LY294002 group（n=12）.The rats in liraglutide group were intraperitoneally injected with liraglutide， while the rats in liraglutide+LY294002 group were intraperitoneally injected with LY294002 in advance and then intravenously injected with liraglutide 30 min later； the rats in normal control group and model group were intraperitoneally injected with equal amount of saline， once a day for each group. After 8 weeks of treatment， the body weights of rats in various groups were determined， and the urinary albumin to creatinine ratios （UACR） and the levels of fasting blood glucose （FBG）， serum creatinine （Scr）and blood urea nitrogen （BUN） of the rats in various groups were detected. HE staining was used to observe the pathomorphology of kidney tissue of the rats in various groups. The expression levels of Synaptopodin protein in the podocytes of the rats in various groups were detected by immunohistochemistry method. The morphology of podocytes in kidney tissue of the rats were observed by electron microscope. The expression levels of Synaptopodin and phosphatidylinositol 3 kinase/ protein kinase B（PI3K/Akt） signaling pathway related proteins in kidney tissue of the rats in various groups were detected by Western blotting method.

Compared with normal control group， the body weight of rats in model group was significantly reduced （P<0.05）， UACR， FBG， Scr and BUN levels were significantly increased （P<0.05）； compared with model group， UACR， FBG， Scr and BUN levels of the rats in liraglutide group were significantly decreased （P<0.05）. The HE staining results showed that the glomerular volumes in model group were enlarged and mesangial cells and matrix were increased， while the pathomorphologic changes in kidney tissue in liraglutide group were significantly ameliorated compared with model group. The immunohistochemical staining results showed that compared with normal control group， the expression level of Synaptopodin protein in the podocytes in kidney tissue of the rats in model group was significantly decreased （P<0.05）.Compared with model group， the expression level of Synaptopodin protein in podocytes in kidney tissue of the rats in liraglutide group was significantly increased （P<0.05）. In normal control group， the podocytic processes covered the outer surface of the glomerular basement membrane with normal shape and uniform distribution； in model group， the podocytic processes were widened， swollen and fused extensively， and some of the podocytic processes disappeared with lysosomal necrosis and renal interstitial edema； the podocytic processes in liraglutide group were swollen and fused better， and the structures of the podocytic processes were similar to those in normal control group. The Western blotting results showed that compared with normal control group， the expression levels of Synaptopodin， PI3K and p-Akt proteins in kidney tissue of the rats in model group were significantly decreased（P<0.05）；compared with model group， the expression levels of Synaptopodin， PI3K and p-Akt proteins in kidney tissue of the rats in liraglutide group were significantly increased （P<0.05）； compared with liraglutide group， the expression levels of Synaptopodin， PI3K and p-Akt proteins in kidney tissue in liraglutide + LY294002 group were significantly decreased （P<0.05）.

Liraglutide can improve the renal function and alleviate the podocyte injury in the rats with DN by activating PI3K/p-Akt signaling pathway.