Sinensetin is a rare polymethoxylated flavone found in certain citrus fruits. In this study, we investigated the effects of sinensetin on lipid metabolism in mature 3T3‐L1 adipocytes. Sinensetin decreased the expression of sterol regulatory element‐binding protein 1c (SREBP1c), suggesting its antiadipogeneic property via downreguation of SREBP1c. Also, sinensetin increased the phosphorylation of protein kinase A and hormone‐sensitive lipase, indicating its lipolytic property via a cAMP‐mediated signaling pathway. Moreover, sinensetin inhibited insulin‐stimulated glucose uptake by decreasing the phosphorylation of insulin receptor substrate and Akt. Furthermore, sinensetin increased the phosphorylation of AMP‐activated protein kinase (AMPK) and acetyl‐CoA carboxylase. It also upregulated mRNA expression of carnitine palmitoyltransferase‐1a, suggesting that sinensetin enhances fatty acid β‐oxidation through the AMPK pathway. Taken together, these results suggest that sinensetin may have potential as a natural agent for prevention/improvement of obesity. Copyright © 2012 John Wiley & Sons, Ltd.