Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes and improves hyperglycemia and insulin resistance in obese (ob) diabetic ob/ob mice. We investigated the effects of nobiletin on lipid metabolism and accumulation of body fat in rats. The control group was fed a 20% high-fat diet and 1% cholesterol, and the nobiletin group was fed same diet supplemented with 0.1% (w/w) nobiletin. The rats were fed for 4 weeks. Weights of epididymal, perirenal, total white adipose tissues (WAT: mesenteric, perirenal, and epididymal), and the subcutaneous WAT in the nobiletin group were significantly lower than those in the control group. This decrease was brought about by nobiletin without affecting triglyceride (TG) levels in the liver and skeletal muscle. Plasma TG levels tended to be decreased by nobiletin. The size and diameter of WAT adipocytes in the nobiletin group were significantly lower than those in the control group. This decrease may be partly due to lower lipoprotein lipase (a major determinant for the development of obesity) levels in WAT of the nobiletin group than that of the control group. Plasma levels of high density lipoprotein cholesterol and apolipoprotein A-I increased significantly with administration of nobiletin. These results suggested a beneficial effect of nobiletin on lipid metabolism. However, no significant differences were observed between the nobiletin and the control groups in proteins such as ATP-binding cassette transporter A1, and sterol regulatory element-binding protein-1 in the liver, PPARγ and tumor necrosis factor-α (TNF-α )i n WAT, and adiponectin and TNF-α in plasma.