Introduction: Mesenchymal stem cell (MSC) is capable of differentiating into many cell lineages including endothelial cell. During the developmental process, embryonic cells are exposed to blood flow generated by the beating heart. Hypothesis: We assessed the hypothesis that shear stress modulate the differentiation of endothelial cell from bone marrow (BM) MSC and enhance the angiogenesis in ischemic model. Methods: BM mononuclear cells of C57/BL6 mouse were isolated and cultured. Seven passage of MSC were exposed to oscillatory, unidirectional laminar shear stress by cone-and- plate device. After shear stress, cells were cultured for seven days until analysis. RT-PCR and immunocytochemistry were performed to determine the endothelial-specific markers. To investigate the therapeutic potential of modified MSC for vascular regeneration, we injected MSC (1x105 cells; n=10), shear stressed MSC (SS-MSC) (1x105 cells; n=10) and saline (n=10) into the thigh muscle immediately after one femoral artery resected mice. Results and Conclusions; SS-MSC promotes the expression of angiopoietin-1, Flk-1, Flt-1, VE-cadherin, PECAM-1, VWF, KDR, eNOS, and CD31 as endothelial cell marker by RT-PCR and immunocytochemistry. The total length of tube of SS-MSC was significantly increased than MSC in Matrigel gel by 60 times (p<0.001). Cyclooxygenase 2 specific inhibitor, NS-398, impaired the ability of MSC to form capillary-like structures by about 30% (p<0.001). PGE2 reversed the inhibition of in vitro angiogenesis caused by NS-398 by about 70 % (p<0.001). Examination of hindlimb perfusion by laser Doppler perfusion image analyses were performed on day 0 and 28. The ratio of ischemic/normal limb blood flow significantly improved in transplantation with SS-MSC mice by 55% and MSC mice by 48% compared with saline treated mice (p<0.001). Capillary density of ischemic muscle was markedly increased in mice receiving SS-MSC and MSC compared with saline treated control mice (495짹98, 453짹83, 218짹37, respectively; p<0.001). In conclusion, physiologic shear stress accelerated to induce MSC to endothelial cell. Therefore modified MSC by shear stress enhance angiogenesis and improve limb salvage in mouse hindlimb ischemic model.