Objective：The present study aims to investigate the role of protease - activated receptor 2(PAR2)in the regulation of human endothelial progenitor cell(EPC)function. Methods：EPCs were stimulated with tryptase(a natural agonist of PAR2)，SLIGKV- NH2(a synthetic agonist of PAR2)and FSLLRY-NH2(an antagonist of PAR2). Cell proliferation and migration were evaluated by EdU incorporation and Transwell model. Expression of the cytokines and receptors were estimated by real - time quantitative PCR and ELISA. Level of intercellular Ras homolog family member A(RhoA)was assessed by Western blot analysis. And RhoA antagonist Y- 27632 was also applied to determine whether the effects of PAR2 activation can be abolished by RhoA inhibition. Results：The agonists of PAR2 dramatically inhibited EPCs proliferation and migration in a dose - dependent manner(P ＜ 0.05). PAR2 activation markedly suppressed the expression of vascular endothelial growth factor-A，vascular endothelial growth factor receptor-2，stromal cell- derived factor -1and C -X -C chemokine receptor type 4(P ＜ 0.05). All these effects can be abolished by the PAR2 antagonist(P ＜ 0.05). PAR2 activation increased the level of RhoA in EPCs，which was also repressed by FSLLRY-NH2(P ＜ 0.05). Y-27632 notably reversed the influence of PAR2 activation on EPCs proliferation and migration(P ＜ 0.05). Conclusion：The activation of PAR2 blunted EPCs proliferation and migration via RhoA signal，hinting a potential role of PAR2 as a novel target for the modulation of endothelial regeneration and vasculogenesis.