Adenophora triphylla var. japonica (Campanulaceae) is known to have anti-inflammatory and anti-tussive effects. Dysfunction of adipocytes and adipose tissue in obesity is related to various inflammatory cytokines or adipokines. In this study, we investigated whether lupenone isolated from A. triphylla var. japonica extract inhibits adipocyte differentiation and expression of adipogenic marker genes in 3T3-L1 preadipocytes. We demonstrated that lupenone resulted in a significant reduction in lipid accumulation and expression of adipogenic marker genes in a dose-dependent manner. In addition, lupenone decreased the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ) induced by troglitazone, and we also demonstrated that lupenone suppressed the PPARγ and CCAAT-enhancer-binding protein α (C/EBPα) protein levels. These findings demonstrated that lupenone isolated from A. triphylla var. japonica extract effectively inhibited adipocyte differentiation through downregulation of related transcription factor, particularly the PPARγ gene. Copyright © 2012 John Wiley & Sons, Ltd.