Abstract--Despite intensive investigation, the molecular mechanism by which the angiotensin II type 2 (AT₂) receptor exerts its cellular and physiological actions remains elusive. In the present study, we have used microarray expression analysis to identify genes whose expression was regulated by this receptor and to determine its cellular consequences. Lentiviral vector was used to express the AT₂ receptor in human coronary artery endothelial cells (HCAECs), followed by analysis of expression profiles. We observed 5224 genes regulated in an AT₂ receptor ligand-independent manner in HCAECs expressing the AT₂ receptor. In addition, 1235 genes were differentially expressed in response to the AT₂ receptor-specific ligand, CGP42112A. Validity of the expression profiles was demonstrated by real-time reverse-transcriptase polymerase chain reaction quantitation of 5 genes. Because some of these genes could be linked to the regulation of extracellular matrix association, we studied the effect of the AT₂ receptor on cell migration. Expression of the AT₂ receptor resulted in a 2-fold inhibition of HCAEC migration. Taken together, these observations demonstrate that the AT₂ receptor regulates expression of genes relevant to cell migration, protein processing, intracellular signaling, and DNA repair in both ligand-dependent and ligand-independent manners.