Abstract: Objective 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 BMSCs transplantation in the treatment of diabetes mellitus (DM) with myocardial infarction (MI). Methods In cell experiments,BMSCs were isolated from 3-week-old male SD rats and were divided into 8 groups: group A, low glucose (LG) group (containing 5.5 mmol/L of glucose); group B, high glucose (HG) group (containing 25 mmol/L of glucose); group C, HG+miR-34a mimic group; group D, HG+miR-34a normal control (NC) group; group E, HG+miR-34a inhibitor group; group F, HG+RSV group; group G, HG+RSV+miR-34a mimic group; group H, HG+RSV+miR-34a inhibitor group. The expression of miR-34a was detected by quantitative reverse transcription PCR (RT-qPCR). Western blot was used to detect the expression of P21 and P16 protein. Senescence-associated β-galactosidase assay was used to detect the senescence level of each group. In vivo experiments, 200 g male SD rats were fed with high-fat and high-sugar feed and were injected with STZ to induce type 2 diabetes model, and then coronary artery ligation method was used to establish a model of diabetes combined with myocardial infarction, which was divided into 6 groups: DM group (diabetes group), DM+sham group, DM+MI 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 MI. Echocardiography was used to detect the cardiac function at 1 week and 3 weeks after operation. Results Compared with the LG group, the expression of miR-34a increased in the HG group (P<0.01), and the level of cellular senescence increased (P<0.01). Compared with the HG group, the expression of miR-34a decreased in the HG+RSV group (P<0.01), and the level of cellular senescence was reduced (P<0.01). After RSV pretreatment, no matter miR-34a was overexpressed or inhibited, the expression of P21 and P16 protein decreased (P<0.01 or P<0.05). After RSV pretreatment, the expression of P21 and P16 can be reduced whether miR-34a is overexpressed or inhibited (P<0.01 or P<0.05). Echocardiographic results showed that compared with the DM group, the postoperative left ventricular ejection fraction (LVEF) values of the DM+MI group, DM+MI+LG group, DM+MI+HG group, and DM+MI+RSV group all decreased (P<0.01). Compared with DM+MI group, postoperative LVEF values of the DM+MI+LG group, DM+MI+HG group, DM+MI+RSV group increased (P<0.01 or P<0.05). Compared with DM+MI+HG group, postoperative LVEF values of the DM+MI+RSV group and DM+MI+LG group increased (P<0.01 or P<0.05). Conclusions 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.