Abstract: AIM: To verify that resveratrol (RSV) can reduce the senescence of bone marrow mesenchymal stem cells (BMSCs) under high glucose conditions by regulating miR-34a, thereby improving the effect of transplantation in the treatment of diabetes with myocardial infarction. METHODS: In cell experiments，BMSCs were isolated from 3-week-old male SD rats and divided into 8 groups: LG group (containing 5.5mmol/L of glucose), HG group (containing 25mmol/L of glucose), HG+miR-34a mimic group, HG+miR-34a NC group, HG+miR-34a inhibitor group, HG+RSV group, HG+RSV+miR-34a mimic group, HG+RSV+miR-34a inhibitor group. The ex＜x＞pression of miR-34a was detected by RT-qPCR. Western blot was used to detect the ex＜x＞pression of P21 and P16 protein. Senescence-associated β-galactosidase assay was used to detect the senescence level of each group. In vivo experiments, STZ injection method and coronary artery ligation method were used to establish the model of diabetes mellitus with myocardial infarction. Rats were divided into 6 groups: DM group (diabetes group), DM+sham group, DM+MI group (diabetes combined with myocardial infarction group), DM+MI+LG group (Low glucose BMSCs injection group), DM+MI+HG group ( High glucose BMSCs injection group), DM+MI+RSV group (HG group after RSV pretreatment). Each group was injected with differently treated BMSCs after myocardial infarction. Ultrasound to detect cardiac function one week and three weeks after operation. RESULTS: Compared with the LG group, the ex＜x＞pression of miR-34a increased in the HG group (P<0.001), and the level of cellular senescence increased (P<0.001). Compared with the HG group, the ex＜x＞pression of miR-34a decreased in the HG+RSV group (P<0.001) and the level of cellular senescence was reduced (P<0.001). After RSV pretreatment, the ex＜x＞pression of P21 and P16 can be reduced whether miR-34a is overexpressed or inhibited. (P<0.001, P<0.01, P<0.05). Echocardiographic results showed that compared with the DM group, the postoperative EF values of the DM+MI group, DM+MI+LG group, DM+MI+HG group, and DM+MI+RSV group all decreased (P<0.001). Compared with DM+MI group, postoperative EF values of the DM+MI+LG group, DM+MI+HG group, DM+MI+RSV group increased (P<0.001, P<0.01). Compared with DM+MI+HG group, postoperative EF values of the DM+MI+RSV group and DM+MI+LG group increased (P<0.001, P<0.01). CONCLUSION: RSV pretreatment of BMSCs can reduce the senescence level of BMSCs under high glucose conditions by reducing miR-34a, and can optimize the therapeutic effect of BMSCs on diabetes with myocardial infarction.