Objective To explore the effect of puerarin on the damage of MPC5 cells treated with high glucose and its molecular mechanism. 〖WTHZ〗Methods Mouse podocyte MPC5 were divided into control group, model group, low, medium and high dose puerarin group, anti-miR-NC group, anti-miR-370 group, high dose puerarin+miR-NC group and high dose puerarin+miR-370 group. Flow cytometry was used to detect cell apoptosis. Western blot was used to detect protein expression. The real time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression of miR-370. Results Compared with the control group, the MPC5 cells apoptosis rate of the model group was increased, the expression of p62 was increased, the expression of LC3-Ⅱ/LC3-Ⅰ was decreased, and the expression of miR-370 was increased (P＜0.05). Compared with the model group, in the low, medium, and high dose puerarin group, the MPC5 cells apoptosis rate was decreased, the expression of p62 was decreased, the expression of LC3-Ⅱ/LC3-Ⅰ was increased, and the expression of miR-370 was decreased, in a dose-dependent manner (P＜0.05). After interfering with the expression of miR-370, the MPC5 cells apoptosis rate was decreased, the expression of p62 was decreased, the expression of LC3-Ⅱ/LC3-Ⅰ was increased (P＜0.05). Overexpression of miR-370 reversed the effects of puerarin on the apoptosis and autophagy of MPC5 cells treated with high glucose. Conclusion Puerarin may reduce the damage of MPC5 cells caused by high glucose by down regulating the expression of miR-370.