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Background and purpose With the increase of age,increased susceptibility to apoptosis and senescence may contribute to proliferative and functional impairment of endothelial progenitor cells (EPCs).The aim of this study was to investigate whether salidroside (SAL) can induce angiogenic differentiation and inhibit oxidative stress induced apoptosis in bone marrow derived EPCs (BM-EPCs),and,if so,through what mechanism.Experimental approach BM-EPCs were isolated and treated with different concentrations of SAL for up to 4 d.Cell proliferation,migration,and tube formation ability were detected by DNA content quantification,transwell assay and Matrigel-based angiogenesis assay.Gene and protein expression were assessed by qRT-PCR and Western blot,respectively.Key results Treatment with SAL promoted cellular proliferation and angiogenic differentiation of BM-EPCs,and increased vascular endothelial growth factor and nitric oxide secretion,which in turn mediated the enhancement of angiogenic differentiation of BM-EPCs.Furthermore,SAL significantly abrogated hydrogen peroxide (H2O2)-induced cell apoptosis,reduced the intracellular level of reactive oxygen species (ROS) and restored the mitochondrial membrane potential of BM-EPCs.Moreover,SAL stimulated the phosphorylation of Akt,mTOR and p70 S6 kinase,as well as ERK1/2,which is associated with cell migration and capillary tube formation.Additionally,SAL reversed the induced effect of H2O2 on phosphorylation of JNK and p38 MAPK,and suppressed the Bax/Bcl-xL ratio after H2O2 induction.Conclusions and implications These findings identify novel mechanisms that regulate EPC function and suggest SAL to be a potential new agent to enhance vasculogenesis as well as protect against oxidative endothelial injury.