To investigate the molecular mechanisms of the antiobese effect of raspberry ketone against high-fat diet fed rats. Methods: Fifty adult male rats were randomly assigned to receive a standard diet, a high fat diet, and the high-fat diet and 0.5%, 1% or 2% raspberry ketone. Body weight, biochemical parameters and gene expression of CCAAT enhancer-binding protein (C/EBP)-d, fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), peroxisome proliferator-activated receptor alpha (PPAR-a), hormone-sensitive lipase (HSL) and hepatic carnitine palmitoyltransferase 1 A (CPT1A) were investigated. Results: Body weight, blood glucose, insulin, total lipids, triacylglycerols, total cholesterol and low-density lipoprotein cholesterol were increased in high-fat diet fed rats. These high fat diet-induced changes were attenuated by treatment with raspberry ketone. High-density lipoprotein cholesterol was decreased in highfat diet fed rats but increased in rats treated with raspberry ketone. Molecular investigations showed induction of gene expression of C/EBP-d , FAS, ACC, CPT1A and inhibition of gene expression of PPAR-a and HSL in high-fat diet fed rats as compared with control. Raspberry ketone treament reversed these changes except CPT1A. Conclusions: Raspberry ketone can prevent obesity induced by a high-fat diet in rats by induction of the expression of enzymes, controlling lipolysis and fatty acids b oxidation as well as inhibition of gene expressions of adipogenic factors.