Cyclic phosphatidic acid (CPA) is found in cells from slime mold to humans and has a largely unknown function. We previously reported that cPA significantly inhibited the lipid accumulation in 3T3-L1 adipocytes through inhibition of PPAR gamma activation. We find here that CPA reduced intracellular triglyceride levels and inhibited the phosphodiesterase 3B (PDE3B) expression in 3T3-L1 adipocytes. PPAR gamma activation in adipogenesis that can be blocked by treatment with cPA then participates in adipocyte function through inhibition of PDE3B expression. We also found the intracellular cAMP levels in 3T3-L1 adipocytes increased after exposure to cPA. These findings contribute to the participation of cPA on the lipolytic activity in 3T3-L1 adipocytes. Our studies imply that CPA might be a therapeutic compound in the treatment of obesity and obesity-related diseases. (C) 2010 Elsevier Inc. All rights reserved.