Aim To determine the consequences of hypoxia inducible factor-1α(HIF-1α)-modified endothelial progenitor cells(EPC) on neovascularization in vivo and discussed the possible mechanisms of homing. Methods Adenovirus mediated human HIF-1α(Ad-HIF-1α) were transduced in human EPC in vitro.To determine if such transduced EPC may facilitate therapeutic neovascularization,heterologous EPC transduced with adenovirus encoding HIF-1α were administered to Balb/c nude mice with hindlimb ischemia.Exogenous EPC homing was observed and the possible mechanism of EPC homing was explored. Results Adenovirus mediated green fluorescence protein(GFP) was consistently expressed in EPC.A significantly higher capillary/myocyte ratio in mice transplanted with Ad-HIF-1α-EPC than in those receiving Ad-GFP-EPC at each time point was found.HIF-1α mRNA and protein expression in the ischemia zone was enhanced(p<0.05).Stromal derived factor(SDF) and CXCR4 upregulation were accompanied by paralleled vascular endothelial growth factor(VEGF) upregulation(p<0.05). Conclusions In vivo,gene-modified EPC facilitate the strategy of cell transplantation to augment naturally impaired neovascularization in an animal model of experimentally induced limb ischemia.The recruitment of EPC may be due to the inducement of SDF,CXCR4 and the VEGF induction may contribute to the EPC proliferation.