Aim To investigate the therapeutic effect of tissue plasminogen activator(t-PA) gene modified umbilical cord blood endothelial progenitor cells (EPCs) transplantation on acute myocardial infarction in rats. MethodsEPCs were expanded in vitro,the slow virus expression vector of t-PA gene was transfected into endothelial progenitor cells to establish rat myocardial infarction model,the experiment was randomly divided into 4 groups:PBS solution group, EPCs group transfected with empty vector, simple EPCs group and EPCs group transfected with t-PA gene. Transplantation was started after acute myocardial infarction 3h in rats, t-PA EPCs group, EPCs group, and empty vector EPCs group were injected with T-PA gene-transfected EPCs, EPCs, and empty vector EPCs. Four weeks after transplantation, cardiac function were evaluated by echocardiography and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) expression level was detected,then the expression levels of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-2/matrix metalloproteinase-9 (MMP-2/MMP-9) and Tissue inhibitor of metalloproteinase(TIMP) in myocardial tissue were detected by Western-blot. Eight hours after transplantation, the expression of t-PA, D-Dimer, fibrin degradation products(FDP), plasminogen activator inhibitor 1 (PAI-1) and fibrinogen (Fib) in serum was detected by ELISA. Results Compared with PBS solution group, empty carrier EPCs group and simple EPCs group,the effect of t-PA gene modified EPCs was the most significant in improving various parameters of cardiac function in rats with acute myocardial infarction. The expression level of NT-Pro-BNP in t-PA EPCs group was significantly lower than that in other groups. The expression level of VEGF and TIMP in t-PA EPCs group was significantly higher than that in other groups. On the contrary, the expression level of metalloproteinase (MMP-2/MMP-9) was significantly lower than that of other groups. The expressions of t-PA and D-dimer in t-PA EPCs group were significantly higher than those in other groups, while PAI-1 and fibrinogen were significantly lower than those in other groups. Conclusions t-PA gene modified EPCs transplantation can effectively treat acute myocardial infarction in rats. Its specific therapeutic effect is related to improving cardiac function, promoting angiogenesis, inhibiting ventricular remodeling, inhibiting thrombosis or increasing thrombolysis.