Aim To clarify the pathological effects and mechanisms of cellular repressor of E1A stimulated gene(CREG) on tumor necrosis factor-α(TNF-α) stimulated vascular endothelial cell(VEC) injury.Methods CREG overexpressed(VC) and knocked-down(VS) human artery VEC were produced and cells were exposed to TNF-α(10 μg/L).Interleukin-6(IL-6) secretion from cells was determined by enzyme immunolinked assay(ELISA).Filamentous actin(F-actin) stress fibre were detected by Rhodamin-Phalloidin staining.Endothelial permeability was detected by measuring the flux of biotin labeled albumin across the EC monolayers.Nuclear factor-κB(NF-κB) expressions and translocalization were examined by Western blot analysis and immunofluorescence.Results After TNF-α stimulation,ELISA showed that IL-6 expression and secretion in VS cells was markedly increased as well as F-actin cytoskeleton rearrangement.Meanwhile,the permeability of VS cells was detected enhanced obviously.Conversely,overexpression of CREG inhibited the secretion of IL-6,F-actin stress fibre formation and hyperpermeability induced by TNF-α in VC cells. Moreover,immunoflurosence and Western blot showed that NF-κB transiently translocated into the nuclei of VC cells,followed by quick exportation into the cytoplasm.Corresponding changes in the pattern of its expression was also observed.However,the expression of NF-κB in CREG knocked-down VS cells was more sustainably elevated and retained in the nuclei.Conclusions CREG can inhibit NF-κB expression,combat TNF-α-induced inflammatory responses and the hyperpermeability of VEC,and thereby antagonize pathological cellular injury.