Trans-cinnamic acid (tCA) is a phenylpropenoic acid, which occurs naturally in a number of plants. In this study, the anti-obese effects of tCA were evaluated in oleic acid (OA)-induced HepG2 cells and high fat diet (HFD)-fed mice. The results showed tCA treatment significantly decreased lipid accumulation in HepG2 cells exposed to OA. Furthermore, administration of tCA (40 mg/kg/day) curbed body weight gains, reduced liver and adipose tissue weight, and ameliorated hepatic steatosis and adipose hypertrophy in mice fed with HFD. In addition, significant decrease in plasma levels of TG, TC and LDL-C were also observed in HFD-fed mice with tCA treatment. Collectively, tCA may play a vital role in preventing and treating diet induced obesity.