Objective Vaspin is an adipocytokine recently identified in the visceral adipose tissue of diabetic rats and having anti-diabetic and antiatherogenic effect. We hypothesized that vaspin may prevent inflammatory cytokine induced-nuclear factor (NF)- κB activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells. Methods We examined the effects of vaspin on NF- κB activation, as well as the expression of NF- κB-mediated genes, such as vascular cell adhesion molecule-a (VCAM-1), intercellular adhesion molecules-1 (ICAM-1), and E-selectin as well as monocyte chemoattractant protein-1 (MCP-1). We used human aortic endothelial cells (HAECs). Tumor necrosis factor-α (TNF-α) was used as a representative atherogenic cytokine. Results Treatment of vaspin significantly increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), the down-stream target of AMPK. Furthermore, treatment of vaspin significantly decreased the TNF-α induced activation of NF-κB as well as the expression of adhesion molecules including VCAM-1, ICAM-1, E-selectin and MCP-1, which effects were abolished after the transfection of small interfering RNA specific to AMPKα1. In adhesion assay using THP-1 cells, vaspin reduced the TNF-α-induced monocyte adhesion to HAECS in AMPK-dependent manner. Conclusion In the light of these findings, we suggest that vaspin might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF- κB following AMPK activation.