Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-alpha-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipocytes. Resveratrol was found to inhibit TNF-alpha-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-alpha-induced MCP-1 transcription. Nuclear factor (NF)-kappaB was determined to play a major role in the TNF-alpha-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-kappaB complex and subsequently suppressed NF-kappaB transcriptional activity in TNF-alpha-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies.