The effect and mechanisms of DNJ on high-fat diet-induced obese mice were investigated， aiming to provide theoretical basis for the development of health food. Obesity model of mice were established by high fat diet， then all mice were treated with DNJ by oral gavage at different doses for 40 d. Then， the serum- and liver-related indicators were determined. Compared with the high-fat control group， 8.0 mg/kg bw/d of DNJ treatment significantly reduced the weight， abdominal fat factor， content of liver fat， and the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C） and free fatty acid （FFA）， visfatin （P＜0.05）. 8.0 mg/kg bw/d of DNJ treatment also significantly increased content of high density liptein cholesterol （HDL-C）， adiponectin （ADP） （P＜0.05）， reduced the activity of enzymes involved in promote fat synthesis fatty acid synthetasein （FAS） and acetyl Coa carboxylasec （ACC）， and significantly increased activity of enzymes in decomposition related Acyl-CoA oxidase （ACO） and carnitine palmitoyl transferase-1 （CPT-1） （P＜0.05）. Conclusion： DNJ could regulate lipid metabolism in obese mice by inhibiting fat synthesis and promote its decomposition through controlling the secretion of adipokine and the activity of enzyme related with lipid metabolism.