The study was conducted to investigate the effects of dietary calcium and soy isoflavone on body fat and lipid metabolism in high fat-induced obesity. Four week old female C57/BL6J mice, known as a good model of diet-induced obesity, were fed low Ca and high fat diet for 6 weeks. After induced obesity, mice were divided into six groups according to diets varying calcium contents (0.1 or 1.5%) and genistein contents (0 or 500 or 1,000 ppm). Body weight, fat pad (perirenal fat and parameterial fat), adipocyte size, serum total lipid and total cholesterol were significantly decreased by both high Ca intake and genistein supplementation. However, the effect of genistein supplementation showed in low Ca-fed groups. Serum LDL-cholesterol and TG were significantly decreased by high Ca intake and genistein supplementation, respectively. In liver, lipogenic enzymes (fatty acid synthase and malic enzyme) activity and TG were significantly decreased by both high Ca intake and genistein supplementation. This inhibitory effect of genistein on lipogenic enzymes showed in low Ca-fed groups. But liver total cholesterol and total lipid were significantly decreased by high Ca intake and genistein supplementation, respectively. Fecal excretion of total lipid, total cholesterol and TG were significantly increased by high Ca intake, not by genistein supplementation. In conclusion, high calcium intake and genistein supplement may be beneficial for suppression of obesity through direct anti-adipogenesis by decreasing fat weight and size and indirect anti-lipo-genesis by inhibiting lipogenic enzymes activity and improving lipid profile.