To evaluate the effects of compound whole grains on high fat and cholesterol diet-induced obesity and lipid accumulation in rats and the possible molecular mechanisms, 40 male Sprague-Dawley rats were randomly assigned to four different diets, including reference chow diet (RCD), high fat and cholesterol diet (HFCD), city diet (CD) and compound whole-grain diet (CWD). Serum lipid profiles and glucose level were examined after 8 weeks. The molecular mechanisms underlined the effects of CWD on lipid metabolism were investigated by western blot and real-time PCR. CD exhibited fat accumulation increasing, increase in serum triacylglycerol, total cholesterol, glucose and the decrease in high density lipoprotein cholesterol. However, CWD can improve blood lipid and blood sugar levels, and at the same time improve obesity and fat accumulation in rats. CWD significantly augmented the relative level of peroxisome proliferators-activated receptor γ (PPARγ) and suppressed the sterol regulatory element-binding protein 1c (SREBP-1c) protein expression in rats’ tissues. Compound whole-grain ameliorates diet-induced obesity and hyperlipidemia by enhancing PPARγ and reducing SREBP-1c in rats.