Obesity is associated with a low-grade inflammation in adipose tissue resulting from increased production of pro-inflammatory cytokines and which call subsequently contribute to the development of insulin resistance. However, the mechanisms underlying the transcriptional regulation of pro-inflammatory genies are Still Unclear. Here we show that tumor necrosis factor (TNF)-alpha treatment attenuated Akt-dependent phosphorylation of Foxol and enhanced transcriptional activity of Foxo1. We found that Foxo1 increased the expression of CCAAT/enhancer binding protein (C/EBP beta a positive regulator of monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-6 genes, through directly binding to its promoter. Furthermore, knockdown of Foxol as well as C/EBP beta inhibits TNF-alpha-induced expression of MCP-1 and IL-6 in 3T3-L1 adipocytes. These findings suggest that activation of Foxo1 triggered by TNF-alpha up-regulates the expression of C/EBP beta in 3T3-L1 adipocytes, thereby leading to all increased production of pro-inflammatory cytokines, MCP-1 and IL-6. (c) 2008 Elsevier Inc, All rights reserved.