Abstract: AIM:To explore whether the transplantation of rat bone marrow mesenchymal stem cells (BM-MSCs) pretreated by endothelial cell specific molecule-1 (ESM-1) into myocardial infarction (MI) rats can increase the stem cell survival and improve the heart function of MI rats. METHODS: ESM-1-pretreated and BrdU-marked MSCs were injected by syringe from epicardial tissue surrounding the infarcted myocardium in Sprague Dawley (SD) rats. Thirty SD rats were randomly divided into three groups: blank group, control group and preconditioning group, with ten rats in each group. Four weeks after myocardial infarction and 4 weeks after cell transplantation, ultrasonic parameters were, respectively, detected in each group. The detected parameters included left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT). ELISA method was used for quantitative detection of serum brain natriuretic peptide (BNP) secretion and the survival of the transplanted cells. RESULTS: Four weeks after cell transplantation, LVESD and LVEDD were reduced, LVEF increased and the content of BNP in plasma decreased in preconditioning group, with statistical significance between preconditioning group and control group (P<0.01). The number of BrdU+cells around infarcted myocardium in preconditioning group significantly increased compared with that in control group (P<0.01). CONCLUSION: ESM-1 incubated with MSCs can activate MSCs and promote their proliferation and differentiation, thus improving heart function.