Vasculogenesis is referred to new vessel formation from vessel forming progenitor cells and the adhesion of endothelial progenitor cell (EPC) to endothelial cell (EC) is essential for it. CXCR4 and 棺2-integrin on EPC, which are the counterpart molecules of stromal cell derived factor (SDF-1) and ICAM-1 on EC, are known to be important in this step and hypoxia is a well known factor driving the EC to express both SDF-1 and ICAM-1 on its surface. Here, we report that endogenous integrin-linked kinase (ILK) in EC is a novel intracellular molecule responding to hypoxia, regulating the selective homing of EPC to ischemic areas through activation of SDF-1 and ICAM-1. The endogenous level of ILK was time-dependently upregulated in EC in response to hypoxia, which was associated with increased SDF-1 and ICAM-1 production in vitro and in vivo. Overexpressing ILK in normoxic EC upregulated both ICAM-1 and SDF-1 whereas blocking ILK in hypoxic EC significantly abrogated the expression of both molecules, which lead to significant attenuation of EPC incorporation into EC in vitro. This signaling process was mediated by Akt/Erk, HIF-1慣 and also by I觀B棺, NF-觀B. ILK blockade in EC in vivo significantly attenuated EPC recruitment to ischemic vessel and consequently, poor vasculogenesis, whereas ILK overexpression significantly improved neovascularization in vivo. These results demonstrate that ILK is essential for vasculogenesis by controlling the expression of SDF-1 and ICAM-1 in hypoxic EC and that ILK is a novel responder to hypoxic stress in EC.