Kirenol, a natural diterpenoid compound, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities; however, its anti-adipogenic effect remains to be studied. The present study evaluated the effect of kirenol on anti-adipogenesis through the activation of the Wnt/beta-catenin signaling pathway. Kirenol prevented intracellular lipid accumulation by down-regulating key adipogenesis transcription factors [peroxisome proliferator-activated receptor gamma (PPAR gamma), CCAAT/enhancer binding proteins a (C/EBPot,), and sterol regulatory element binding protein-1c (SREBP-1c)1 and lipid biosynthesis-related enzymes [fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC)1, as well as adipocytokines (adiponectin and leptin). Kirenol effectively activated the Wnt/beta-catenin signaling pathway, in which kirenol up-regulated the expression of low density lipoprotein receptor related protein 6 (LRP6), disheveled 2 (DVL2), beta catenin, and cyclin D1 (CCND1), while it inactivated glycogen synthase kinase 3f3 (GSK313) by increasing its phosphorylation. Kirenol down-regulated the expression levels of PPARy and C/EBPa, which were up-regulated by siRNA knockdown of 13-catenin. Overall, kirenol is capable of inhibiting the differentiation and lipogenesis of 3T3-L1 adipocytes through the activation of the Wnt/13-catenin signaling pathway, suggesting its potential as natural anti-obesity agent. 2014 Elsevier Inc. All rights reserved.