Aim To treat myocardial infarction(MI) with bone marrow mesenchymal stem cell(MSC) transplantation combined with vascular endothelial growth factor(VEGF) gene therapy in rabbits and to study its mechanisms. Methods Forty-eight rabbits were randomly divided into MI group(n=12),MSC group(n=12),VEGF group(n=12),MSC+VEGF group(M+V group,n=12).Rabbit myocardial infarction models were founded by the ligation of left anterior descending artery.10~7 MSC were injected into the infarct-zone in four sites 2 weeks later in MSC and M+V group.phVEGF gene were injected in infarct-zone in VEGF group and MSC transfected with phVEGF gene were injected in M+V group.Heart function including LVEDP,LVSP,LVDP,-dp/dtmax,+dp/dtmax,were measured in vivo.The hearts were harvested at 4 weeks after transplantation and sectioned for HE stain,immunohistochemical stain of BrdU and Ⅷ factor antigen. Results The left ventricular hemodynamics parameters showed that heart function were improved more in M+V group than MSC group,MI group and VEGF group. The numbers of BrdU posivtive cell in M+V group(61.24±8.51)were more than in MSC group(44.21±7.68,p<0.01).The numbers of vessels in infarcted zone were more in M+V group(48.75±7.96) than in MSC group(33.08±6.12,p<0.01),VEGF group(29.98±8.04,p<0.01)and MI group(18.32±3.88,p<0.01). Conclusions VEGF gene transfected MSC transplantation could improve heart function after myocardial infarction,and they were more effective than sole MSC transplantation.Keeping more MSC survival and ameliorating the blood supply of infarct-zone might be involved in the mechanisms.