This study was carried out to determine the action mechanism of sulfur-grain larvae extract (SGE) on anti-obesity and the reduction of blood lipid level in high-fat diet induced obese model animals. Animals were classified into a normal diet group (NC, normal control), HFD (high-fat diet without SGE), HFD 15 (high-fat diet + oral administration of 15 mg of SGE extract per 100 g body weight) and HFD 30 (high-fat diet + oral administration of 30 mg of SGE extract per 100 g body weight). The body weight gain declined in HFD 15 and HFD 30 groups compared with the HFD group, even though the diet intake increased significantly. The weight of liver and adipose tissue increased significantly in HFD group compared with in the HFD 15 and HFD 30 groups. Triglyceride, total cholesterol, LDL-C and AI decreased in HFD 15 and HFD 30 groups compared with in the HFD group, but the contents of HDL-C increased significantly. Expression of SREPB-1α, SREPB-2 mRNA in the liver was lower in the high-fat diet group compared with the HFD group, but the expression of LPL mRNA in adipose tissue and PPARα increased significantly. Fat accumulation in the liver tissues and liver damage were greatly reduced in HFD 15 and HFD 30 groups compared with in the HFD group. The size of adipocytes became smaller in the HFD 15 and HFD 30 groups compared with HFD group. In conclusion, this research discovered for the first time that grain maggot has anti-obesity effects, by reducing the abdominal fat of obese model animals and lowering blood lipid level through the down-regulation of PPAR-1α and SREPB-2 mRNA and the up-regulation of PPAR-α mRNA.