Background & Aim: Ischemia leads to disruption of cell-to-cell, cell-to-extracellular matrix (ECM) interaction and angiogenesis is a physiologic response to hypoxia involving dynamic interaction between cells & ECM. Integrin-linked kinase (ILK) is a 59kDa cytoplasmic Ser/Thr kinase that binds to the cytoplasmic domain of 棺1, 棺3-integrin. Since ILK is a downstream molecule of integrin signaling, it provides a good potential for a candidate molecule in promoting angiogenesis. Here, we investigated the role of ILK in response to hypoxia and its effect on angiogenesis. Methods & Results: (1) Confirmation of basal ILK expression in HUVEC under hypoxia : ILK was continuously upregulated in a time-dependent manner by hypoxia in immunoblot. (2) Effect of ILK overexpression in HUVEC : Adenovirus-mediated ILK overexpression in HUVEC resulted in upregulation of p-Akt, p-Erk1/2, HIF-1慣 & ICAM-1. The upregulation of HIF-1慣 & ICAM-1 was attenuated with Erk inhibition by PD98059 and PI3K/Akt inhibition by LY294002 compound. ICAM-1 upregulation was also inhibited by YC-1, a chemical inhibitor of HIF-1慣. (3) Effect of ILK on HUVEC apoptosis : HUVEC was transfected with adenovirus encoding GFP or wild-type ILK (WT-ILK) and exposed to hypoxia. Apoptosis under hypoxia was attenuated with WT-ILK transfection. (4) Effect of ILK on HUVEC migration : Scratch wound assay was done to examine the role of ILK in endothelial migration in response to VEGF. Migration in response to VEGF was significantly reduced when transfected with KD-ILK whereas ILK overexpression with WT-ILK lead to significantly increased migration even without VEGF. (5) Effect of ILK on tube formation : To examine the role of ILK on endothelial cell differentiation to vascular structure in vitro, Matrigel짰 tube formation assay was done. Tube formation in response to VEGF was significantly reduced when transfected with KD-ILK whereas ILK overexpression with WT-ILK lead to effective tube formation even without VEGF. Conclusion : We found a novel ILK-mediated angiogenic signal under hypoxia involving Erk1/2 or Akt - HIF-1慣 – ICAM-1 and that ILK is a important regulator of angiogenesis by mediating endothelial cell survival, migration and differentiation.