The differentiated mature podocytes were randomly divided into control group， high glucose group， mannitol control group， liraglutide group， high glucose + liraglutide group. The RNA was extracted from cells in each group. Real-time PCR（RT-PCR） was used to detect the expression levels of Nephrin， Podocin and ZO-1 mRNA in the podocytes in various groups. Western blotting method was used to detect the expression levels of Nephrin， Podocin， ZO-1， Bcl-2 and caspase-3 proteins in the podocytes in various groups. The Synaptopodin expression in the podocytes was observed by immunofluorescence method. The apoptotic rate was measured by flow cytometry. The differentiated mature podocytes were randomly divided into control group， high glucose group， high glucose + liraglutide group， high glucose+liraglutide+LY294002 group. The expression levels of the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway proteins were observed by Western blotting method.

Compared with control group， the expression levels of mRNA and protein of the podocytes marker proteins Nephrin， Podocin and ZO-1 in the podocytes in high glucose group were reduced（P<0.05）， the expression level of Bcl-2 proein was reduced（P<0.05）， the expression level of caspase-3 protein was increased（P<0.05）， the fluorescence intensity of specific skeleton protein Synaptopodin was decreased significantly（P<0.05）， and the apoptotic rate of podocytes was increased significantly（P<0.05）. Compared with high glucose group， the expression levels of mRNA and protein of Nephrin， Podocin and ZO-1 in the podocytes in high glucose + liraglutide group were increased（P<0.05）， the expression level of Bcl-2 proein was increased （P<0.05）， the expression level of caspase-3 protein was decreased（P<0.05）， the fluorescence intensity of podocyte specific skeleton protein Synaptopodin was increased significantly（P<0.05）， and the apoptotic rate of podocytes was decreased significantly（P<0.05）. Compared with control group， the expression levels of PI3K and phosphorylated（p-Akt） proteins in the podocytes in high glucose group were decreased significantly （P<0.05）， the expression level of Bcl-2 protein was decreased（P<0.05）， and the expression level of caspase-3 protein was increased（P<0.05）. Compared with high glucose group， the expression levels of PI3K and p-Akt proeins in high glucose + liraglutide group were increased significantly（P<0.05）， the expression level of Bcl-2 proein was increased（P<0.05）， and the expression level of caspase-3 protein was decreased significantly（P<0.05）. Compared with high glucose + liraglutide group， the expression levels of PI3K and p-Akt proteins in the podocytes in high glucose + liraglutide + LY294002 group were decreased（P< 0.05），the expression level of Bcl- 2 protein was decreased（P<0.05），and the expression level of caspase-3 protein was increased（P<0.05）.

Liraglutidecan inhibit the apoptosis of podocytes by activating the PI3K/Akt signaling pathway and alleviates the podocyte injury induced by high glucose.