Tumor necrosis factor alpha (TNF alpha) is known to inhibit adipogenesis, but the molecular mechanism of this inhibition remains elusive. In the present study, we found that TNF alpha-induced inhibition of adipogenesis mainly occurs when 3T3-L1 preadipocytes are treated with TNF alpha within 2 h induction of adipogenesis. We revealed that TNF alpha treatment results in the up-regulation of miR-155 through the NF kappa B pathway in 3T3-L1 cells. This overexpression of miR-155 may suppress the expression of C/EBP beta and CREB by directly targeting their 3' untranslated regions (3' UTRs). Importantly, anti-miR-155 reduces the TNF alpha-induced inhibition of adipogenesis, whereas exogenous expression of mir-155 inhibits adipogenesis. Taken together, these findings reveal a novel role for TNF alpha in the regulation of anti-adipogenic miRNAs. (C) 2011 Elsevier Inc. All rights reserved.