OBJECTIVE:To investigate how and to what extent platycodin saponin (PS) from Platycodi Radix exerts a favorable influence on obesity and hyperlipidemia. DESIGN: Sprague-Dawley rats were fed with a high fat (HF) diet for 4 weeks and then the animals were treated with 35 or 70 mg/kg of PS for another 4 weeks. Changes in body weight and daily calorie intake were measured regularly during the experimental period and the degree of linear correlation for the above two variables was further analyzed. The in vitro lipase inhibition of each PS compound and the in vivo fecal lipid excretion were examined in hope of revealing their relationship. The concentrations of hepatic triglyceride and cholesterol in serum. RESULTS: The body weight reduction (1374% vs HF control, Po0.05) by PS administration was highly correlated to the food intake restriction (Pearson's linear coefficient r ¼ 0.752, Po0.005). The in vitro inhibition of lipase by each isolated compound and mixture of PS were virtually identical. Consequently, the fecal TG excretion was increased by 2.1-3.2 folds depending on the dose of PS. The serum TG and LDL-cholesterol concentrations were decreased without noticeable changes in HDLcholesterol levels. Concomitantly, the contents of the hepatic TG, cholesterol, and the liver surface fat pads were decreased in ubiquity, but no noticeable biochemical abnormalities or histological tissue damages were observed. CONCLUSIONS: The administration of PS produced profound effects on the control of obesity and lipid metabolism, which resulted in LDL-cholesterol reduction. PS also caused a remarkable reduction in calorie intake, which was highly correlated to the body weight loss. These results suggest that PS has a greater role in antiobesity, hypolipidemia, and liver protection than previously thought. Hence, PS could be a potential therapeutic alternative in the treatment of obesity and hyperlipidemia.