Boussingaultia gracilis Miers var. pseudobaselloides Bailey is used as a Chinese folk medicine for treatment of diabetes, inflammation, and liver disease. The present study is to investigate the anti-obesity and hypolipidemic effects of B. gracilis Miers var. pseudobaselloides Bailey ethanol extract (BGE). Six-week-old Sprague–Dawley male rats were separately fed for 6 weeks with two kinds of diets—a normal diet (ND) and a high-calorie high-fat diet (HD). Then the animals were treated with tea catechin (100 mg/kg) or BGE (300, 600, or 900 mg/kg) for another 6 weeks. BGE significantly lowered body weight gain, fat-pad weights, and serum and hepatic lipid levels in HD-induced obese rats. The lipid droplets in hepatic tissue of BGE-treated groups were also markedly lessened compared with HD group rats via oil red O staining. Significant increases were observed in the expressions of genes for peroxisome proliferator-activated receptor (PPAR) α and for fatty acid oxidation and thermogenesis-related proteins—acyl-coenzyme A oxidase, carnitine palmitoyl transferase-1, and uncoupling protein-2—in the liver of the BGE-treated groups. Moreover, BGE was found to suppress the expression of sterol response element binding protein-1, a lipogenic gene, as well as those of fatty acid synthase and PPARγ in adipose tissue and liver of HD group rats. These results indicate that B. gracilis Miers var. pseudobaselloides Bailey may have an anti-obesity and hypolipidemic effect through regulation of expression of genes involved in lipolysis and lipogenesis.