OBJECTIVE To examine the anti-obesity effects of ginsenosides in Korea Red Ginseng (KRG, Panax ginseng) in rats fed with a high-fat diet (HFD). METHODS Twenty-five 4-week-old obesity rats after receiving an HFD for 5 weeks; subsequently, they were additionally treated with ginsenosides Rb1, Rd, Rg1, or Re (10 mg/kg, intraperitoneal injection) for a further 3 weeks (n=5 in each group). The control rats were fed a normal diet. The food consumption, body weight, locomotor activity, serum lipids, adipose tissues, nitric oxide (NO) expression, leptin, neuropeptide Y (NPY), cholecystokinin (CCK) in the brains were measured. RESULTS In the HFD-fed rats, body weight, body fat mass, serum levels of leptin and NO were significantly higher than in the control rats (P<0.05 or P<0.01). However, the treatment of Rd, Re, and Rb1 markedly decreased body fat mass and body weight (P<0.05). The serum level of leptin and NO in ginsenoside-treated rats were markedly lower than the control group (P<0.01). The expression of NPY and CCK in the hypothalamic nuclei showed insignificant difference among groups. However, the expression of NPY immunoreactive neurons in the hypothalamus was significantly reduced in the Rb1-treated group (P<0.05). CONCLUSIONS PD-type ginsenoside Rb1 from the crude saponins of KRG may be a useful compound for the treatment of obesity and related disorders through the modulation of peripheral and central appetite-regulating signals.