Adipose tissue plays a key role in the development of obesity and diabetes. Natural products are one of the main sources for discovering new lead compounds. In the present study, (2S)-7,4'-dihydroxy-8-prenylflavan (DHPF), a natural prenylated flavan isolated from Morus yunnanensis, was found to significantly promote adipogenesis and increase glucose uptake in 3T3-L1 cells. Real-time PCR results showed that DHPF increased the expression of glucose and lipid metabolism-related genes (C/EBP alpha, PPAR gamma, aP2, GLUT4 and adiponectin) and decreased the expression of inflammatory cytokine TNF-alpha. Western blotting further revealed that DHPF activated p38 MAPK at the initial stage of 3T3-L1 preadipocyte differentiation. DHPF-induced activation of p38, adipogenesis and glucose uptake were effectively blocked by SB203580, a specific p38 inhibitor. These results indicate that DHPF could stimulate adipogenesis and increase glucose uptake through the p38 MAPK pathway, and DHPF may be useful for the prevention and treatment of obesity-associated disorders such as type 2 diabetes (T2D). (C) 2015 Elsevier Inc. All rights reserved.