Aim To investigate the protective effect of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside(TSG) on human umbilical vein endothelial cells(HUVEC) apoptosis induced by H_2O_2 and further explore whether this effect is related to the NF-κB signaling pathway and the expression of apoptosis-related protein. Methods HUVEC were divided into three groups: control group,H_2O_2 group and TSG group.The proliferation and apoptosis rates of HUVEC were detected by MTT and flow cytometry respectively.The protein expression of NF-κB p65,IκB and bcl-2 were assessed by Western blot. Results According to the MTT and flow cytometry,the proliferation rate of HUVEC decreased significantly compared with control group(P<0.01),while the apoptosis rate increased obviously(P<0.01) after treating with H_2O_2.The proliferation rate of TSG pretreatment group increased significantly(P<0.01) while the apoptosis rate decreased obviously(P<0.01) compared with H_2O_2 group.Compared with H_2O_2 group,Western blot analysis revealed that the expression of NF-κB p65 was declined and the level of IκB and bcl-2 were increased significantly after pretreated by TSG(P<0.01). Conclusions TSG has a protective effect on the HUVEC apoptosis induced by H_2O_2 and this molecular mechanism may be associated with its inhibiting the activation of NF-κB/IκB signaling pathway and the up-regulating expression of bcl-2 protein.