In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-alpha-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-alpha-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-alpha-activated signal pathway of nuclear factor-kappa B (NF-kappa B) by preventing NF-kappa B inhibitory protein (I kappa B alpha) degradation and NF-kappa B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-alpha-induced ERR activity and ERR phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-alpha-induced NF-kappa B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERR inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-alpha. These results suggest that omentin may inhibit TNF-alpha-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-kappa B pathway. (c) 2012 Elsevier Inc. All rights reserved.