Objective To explore the effect of Potentilla anserina polysaccharide on the injury of glomerular mesangial cells induced by high glucose and its possible mechanism. Methods High glucose was used to induce SV40 MES 13 mouse glomerular mesangial cells to establish a cell injury model, and 0.1, 0.3, 0.6 mg/mL Potentilla anserina polysaccharides were added to treat the cells. pcDNA and pcDNA-circ-AKT3 were respectively transfected into mesangial cells induced by high glucose. si-NC and si-circ-AKT3 were transfected into glomerular mesangial cells induced by high glucose and Potentilla anserina polysaccharide was added to the cells. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialedhyde (MDA) were tested according to the kit. The levels of IL-6, IL-18 and monocyte chemoattractant protein-1 (MCP-1) were detected by ELISA. Flow cytometry was used to detect the apoptosis rate. The real time quantitative PCR was used to detect the expression of circ-AKT3 mRNA. Results In glomerular mesangial cells induced by high glucose, the levels of SOD and GSH-Px were decreased, but the levels of MDA, IL-6, IL-18, and MCP-1 were increased, along with the increased rate of apoptosis, and decreased the expression level of circ-AKT3. After Potentilla anserina polysaccharide treatment of glomerular mesangial cells induced by high glucose, the levels of SOD and GSH-Px were increased whereas the levels of MDA, IL-6, IL-18, and MCP-1 were decreased, together with decreased apoptosis rate, and increased expression level of circ-AKT3. The difference was significant among different concentration groups. pcDNA-circ-AKT3 was transfected into glomerular mesangial cells induced by high glucose, followed by the increased levels of SOD and GSH-Px, with the decreased levels of MDA, IL-6, IL-18 and MCP-1. The apoptosis rate was also reported decreased. Interference of circ-AKT3 expression, on the other hand, can restore the protective effect of Potentilla anserina polysaccharide on high glucose induced glomerular mesangial cell injury. Conclusion Potentilla anserina polysaccharide can alleviate the damage of glomerular mesangial cells induced by high glucose by increasing the expression of circ-AKT3.