Background/Aims: Resveratrol is a naturally occurring polyphenol phytoestrogen and one of several constituents of red wine thought to be cardioprotective. We investigated the effect of resveratrol on the expression of the atherogenic chemokine, monocyte chemotactic protein-1 (MCP-1). Methods: Human umbilical vein endothelial cells were stimulated with interleukin-1β (IL-1β) in the absence or presence of resveratrol. MCP-1 levels were determined by ELISA and MCP-1 mRNA was measured. Results: Resveratrol (1–100 µ M) dose-dependently inhibited IL-1β-stimulated MCP-1 secretion, with ∼45% inhibition at 50 µ M resveratrol. This was a Gi-protein- and NO-dependent effect. Resveratrol also significantly inhibited MCP-1 gene expression in a Gi-protein-dependent but NO-independent manner. While resveratrol had no effect on MCP-1 mRNA degradation, it inhibited MCP-1 promoter activity and reduced nuclear factor ĸB and activator protein-1 binding activity induced by IL-1β. Moreover, while hemoxygenase-1 (HO-1) expression was induced by resveratrol in human umbilical vein endothelial cells, neither treatment with the HO-1 inhibitor tin-protoporphyrin IX nor siRNA-directed knockdown of HO-1 had any effect on the inhibition of MCP-1 mRNA or protein secretion by resveratrol. Conclusion: These data demonstrate an inhibitory effect of resveratrol on MCP-1 synthesis and secretion, mediated via distinct signaling pathways. The inhibition of MCP-1 may represent a novel cardioprotective mechanism of resveratrol.