Background: Recruitment and adhesion of bone marrow (BM)-derived circulating progenitor cells to ischemic tissue are important for vasculogenesis and tissue repair. Recently, we found angiopoietin-1 (Ang-1) is a useful cell-priming agent to improve the therapeutic efficacy of progenitor cells. However, the systemic effect and the underlying mechanisms of Ang-1 on recruitment of BM-derived progenitor cells to foci of vascular injury have not been well defined. Methods and Results: Ang-1 is a critical stimulator of stromal cell-derived factor (SDF-1), the principal regulator of BM-cells trafficking. Furthermore, SDF-1 stimulation by Ang-1 was blocked by siRNA against hypoxia-inducible factor-1(HIF-1慣). Ang-1 increased the synthesis of HIF-1慣 by activating mammalian target of rapamycin (mTOR) in hypoxic endothelium. The intermediate mechanism transmitting Ang-1 signal to downstream mTOR/HIF1慣/SDF-1 pathway was the enhanced binding of Tie2 receptor with integrin-linked kinase (ILK), an upstream activator of mTOR. In mouse ischemic model, local injection of Ang-1 stimulated the incorporation of BM-derived progenitor cells into ischemic limb, thereby enhanced neovasculogenesis and limb salvage. Conclusion: Our findings identify Ang-1/HIF-1慣/SDF-1 pathway as a novel inducer of BM-derived progenitor cells recruitment and neovasculogenesis in ischemic disease.