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Abstract: Background: Clinical trials of vascular endothelial growth factor (VEGF) gene therapy have proven that VEGF has beneficial effects on the ischemic heart disease; however, the lack of a delivery system targeted to the injured myocardium reduces the local therapeutic efficacy of VEGF and increases its possible adverse effects. This study was performed to determine if macrophages transfected with human VEGF165 could incorporate into blood vessels and target to ischemic myocardial tissue to induce neovascularization and improve cardiac function. Methods: Macrophages, macrophages transfected with hVEGF165 or phosphate buffered saline (PBS) were injected intravenously into the mice immediately after coronary artery ligation. Seven days after myocardial infarction (MI), protein expression of VEGF in border zone tissue was quantified by Western blot, and the location of the injected cells was determined by immunofluorescence. Twenty-eight days after MI, capillary density and cardiac function were measured. Results: The level of VEGF expression in the mice injected with macrophages overexpressing VEGF was much higher than that in the mice injected with macrophages or PBS (p< 0.01for both). Macrophages transfected with hVEGF165 could incorporate into the blood vessels. Furthermore, injection of macrophages overexpressing VEGF significantly augmented capillary density and improved cardiac function. Conclusions: Macrophages transfected with hVEGF165 incorporate into blood vessels and act as a carrier of VEGF that can target ischemic myocardial tissue and contribute to neovascularization and improve cardiac function. [Copyright &y& Elsevier]