Our previous studies demonstrated that CD151 gene promoted neovascularization in ischemic heart model. To improve the delivery efficacy and target specificity of CD151 gene to ischemic heart, we generated an adeno-associated virus (AAV) vector in which CD151 expression was controlled by the myosin light chain (MLC-2v) promoter to achieve the cardiac-specific expression of CD151 gene in ischemic myocardium and to limit unwanted CD151 expression in extracardiac organs. The function of this vector was examined in rat ischemic myocardium model. The protein expression of CD151 in the ischemic myocardium areas, liver and kidney was confirmed by using Western blot, while the microvessels within ischemic myocardium areas were detected by using immunohistochemistry. The results showed that MLC-2v significantly enhanced the expression of CD151 in ischemic myocardium, but attenuated its expression in other organs. The forced CD151 expression could increase the number of microvessels in the ischemic myocardium. This study demonstrates the AAV-mediated and MLC-2v regulated CD151 gene is highly expressed in the ischemic myocardium and cardiac-specific delivery that is more efficiently targets CD151 to the ischemia myocardium after myocardial infarction.