Background and Purpose: Obesity has become a major health threat worldwide related to type 2 diabetes, hypertension, cardiovascular disease, etc. Activating brown adipocytes and inducing browning of white adipocytes has been proposed as a potential molecular target for obesity treatment. In the present study, we investigated the effects of emodin on browning in mice with high-fat diet (HFD) and explore its underlying pharmacological mechanisms. Experimental Approach: Male C57BL/6J mice were fed with HFD for 8 weeks to induce obesity. Then the obese mice were divided into four groups randomly, HFD or emodin (40, 80 mg/kg/day) or CL 316243 (1 mg/kg/day) for another 6 weeks. Body weight and food intake were recorded every week. After 6 weeks of treatment, fasting blood glucose, oral glucose tolerance, Lee’s index, weight ratio (fat weight/body weight), blood lipids, and adipose tissues morphology were assayed. Then UCP1, CD36, FATP4, PPARα and PHB protein in subcutaneous white adipose tissue (scWAT) and brown adipose tissue (BAT) were analyzed. In addition, the lipid metabolites in adipose tissues were analyzed by Ultra Performance Liquid Chromatography with Electrospray Ionization Tandem Mass Spectrometry.