Background & Aim: New vessel formation, angiogenesis is the sequential process of attachment-detachment-reattachment of endothelial cells (EC) and dynamic interaction between EC and extracellular matrix (ECM) is critical point. Cell adhesion to ECM is an essential process that controls proliferation, migration and survival of EC. Intergrin-linked kinase (ILK) is a 59KDa cytoplasmic serin/threonin protein kinase and binds to the cytoplasmin domain of ��1 integrin. The implication of ILK, however, has not been investigated in EC. In this study, we show that ILK affected anchorage-dependent cell survival, in floating culture. ILK overexpression also increased cell proliferation and enhanced angiogenesis in matrigel tube formation when reattachment occurred. Methods & Results: (1) Confirmation of ILK expression; When HUVECs were deprived of anchorage by culturing them on a dish coated with polyHEMA (adhesion inhibitor), Endogeneous ILK expression was transiently elevated and then reduced after detachment. ILK expression was also transiently elevated in response to reattachment in Western blot analysis. (2) Effect of ILK overexpression in floating culture; ILK overexpression significantly protected anchorage-deprivation-induced stress (GFP vs ILK=100짹1.0 vs 186.1짹1.4%, p<0.01). (3) Effect of ILK-overexpression in cell signaling pathway; ILK overexpression increased survival signal molecules (phospho-AKT, phospho-GSK) in Western blot analysis. (4) Effect of ILK-overexpression in angiogenesis; ILK overexpression enhanced angiogenesis in matrigel tube formation when reattachment occurred. (5) To determine if such genetic modification may facilitate therapeutic angiogenesis, ILK overexpressed endothelial progenitor cells (EPCs) were administered to athymic nude mice with hindlimb ischemia via systemic infusion. Limb salvage rate and blood flow recovery were both improved significantly and the dose of genetically modified EPCs for limb salvage was several times less than that of native EPCs. Conclusion: These data demonstrate the important role of ILK in EC survival, and suggest a novel candidate gene to protect EC from temporarily detached stress during angiogenesis.