Licorice, the root of Glycyrrhiza glabra, has been reported to exhibit an anti-obesity effect. Here the anti-obesity effect of licorice acetone extract (LE) standardized by glabridin content was examined by oral administration of 50 or 100 mg/kg per day of LE for 12 weeks in C57BL/6N mice with high-fat-diet-induced obesity. Body-weight gain and epididymal fat mass, which were increased by the induction of obesity, were decreased significantly in mice treated with LE. Serum levels of total cholesterol, aspartate aminotransferase, and alanine aminotransferase, in addition to the adipocyte size of epididymal fat and hepatic steatosis, were ameliorated by LE treatment. Furthermore, LE regulated the expression levels of acetyl-CoA carboxylase and peroxisome proliferator-activated receptor gamma in the liver. In particular, LE increased serum adiponectin strongly, which inhibited lipid anabolism and promoted lipid catabolism. These findings suggest that licorice extracted with acetone has anti-obesity effects.