Angiopoietin (Ang) 1 is a ligand forendothelium-specific receptor tyrosine kinase Tie-2. Inadult vasculature, Ang1/Tie2 signaling is thought toregulate both maintenance of vascular quiescence andpromotion of angiogenesis. However, it has beenunknown how Tie2 signal regulates these distinctbiological functions. Recently, we and Alitalo’s grouphave clarified that Ang1 assembles distinct Tie2signaling complexes in either presence or absence ofendothelial cell-cell adhesions. Ang1 induces trans-association of Tie2 at cell-cell contacts, whereas Tie2 isanchored to the extracellular matrix (ECM) by Ang1 atthe cell-substratum interface. Trans-associated Tie2 andECM-anchored Tie2 activate distinct signalingpathways. In this review, we discuss how Ang1/Tie2signal regulates both maintenance of vascular quiescenceand promotion of angiogenesis, especially focusing onthe roles of trans-associated Tie2 and ECM-anchoredTie2