To disclose the anti-atherosclerotic mechanisms of steady laminar shear stress, we analyzed the expression of human inhibitor of apoptosis protein-2 (HIAP-2), whose gene was selected from a cDNA library of sheared endothelial cells (ECs), on ECs. HIAP-2 was dose-independently and time-dependently induced in ECs by shear stress, regulated at the transcriptional level. HIAP-2 expression was also identified in vivo. Shear stress-mediated inhibition of EC apoptosis was associated with the inhibition of caspase-3 activity, suggesting that the shear stress prevents EC apoptosis via negative regulation of caspase-3 by the increment of HIAP-2.