It is noted that chalcone derivatives have characteristic diverse pharmacological properties, and that precise evidence has been growing that they could regulate a tumor necrosis factor-α (TNF-α) induced insulin resistance. The purpose of the present investigation is to elucidate the effects of the identified chalcone derivatives on adipogenesis, and to find the underlying mechanism of action in that case. Consequently, we first investigated whether the chalcone derivatives could affect the identified PPARγ-induced transcriptional activity on the proliferator-activated receptor response elements (PPRE) at target promoters, and find that trans-chalcone most significantly increased the PPARγ -induced transcriptional activity. Additionally, we confirmed that there were up-regulatory effects of trans-chalcone during the adipogenesis and lipid accumulation, and on the mRNA of adipogenic factors in 3T3-L1 cells. Next, we examined the effect of trans-chalcone on the inhibition induced by TNF-α on adipogenesis. To that end, we noted that the treatment with trans-chalcone attenuated the effect of TNF-α mediated secretion of various adipokines that are involved in insulin sensitivity. For this reason, we noted that this study clearly demonstrates that trans-chalcone enhanced adipogenesis, in part, by its potent effect on PPARγ activation and by its reverse effect on TNF-α.