Previous studies demonstrated that both ginseng root and ginseng berry possess anti-diabetic activity. However, a direct comparison between the root and the berry under the same experimental conditions has not been conducted. In the present study, we compared anti-hyperglycemic effect between Panax ginseng root and Panax ginseng berry in ob/ob mice, which exhibit profound obesity and hyperglycemia that phenotypically resemble human type-2 diabetes. We observed that ob/ob mice had high baseline glucose levels (195 mg/dl). Ginseng root extract (150 mg/kg body wt.) and ginseng berry extract (150 mg/kg body wt.) significantly decreased fasting blood glucose to 143 +/- 9.3 mg/dl and 150 +/- 9.5 mg/dl on day 5, respectively (both P < 0.01 compared with the vehicle). On day 12, although fasting blood glucose level did not continue to decrease in the root group (155 +/- 12.7 mg/dl), the berry group became normoglycemic (129 +/- 7.3 mg/dl; P < 0.01). We further evaluated glucose tolerance using the intraperitoneal glucose tolerance test. On day 0, basal hyperglycemia was exacerbated by intraperitoneal glucose load, and failed to return to baseline after 120 min. After 12 days of treatment with ginseng root extract (150 mg/kg body wt.), the area under the curve (AUC) showed some decrease (9.6%). However, after 12 days of treatment with ginseng berry extract (150 mg/kg body wt.), overall glucose exposure improved significantly, and the AUC decreased 31.0% (P < 0.01). In addition, we observed that body weight did not change significantly after ginseng root extract (150 mg/kg body wt.) treatment, but the same concentration of ginseng berry extract significantly decreased body weight (P < 0.01). These data suggest that, compared to ginseng root, ginseng berry exhibits more potent anti-hyperglycemic activity, and only ginseng berry shows marked anti-obesity effects in ob/ob mice.