In this study, we evaluated anti-hyperglycemic effect and body weight reduction activity of Gymnema yunnanense extract in obese ob/ob and diabetic db/db mice. Animals received daily intraperitoneal injections of the extract 100 mg/kg for 12 days. On Day 5, the extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice (161+/-14.5mg/dl versus 238+/-21.5mg/dl, P<0.01). On Day 12, the extract-treated ob/ob mice had normal fasting blood glucose levels, compared with vehicle-treated mice (119+/-3.3mg/dl versus 240+/-12.9 mg/dl, P<0.01). Glucose tolerance improved significantly. This was demonstrated by overall glucose excursion calculated as area under the curve (AUC) during the 2h intraperitoneal glucose tolerance test (IPGTT), which decreased by approximately 22% (P<0.01) compared to vehicle-treated ob/ob mice. In addition, extract-treated ob/ob mice lost weight significantly from 51.7+/-1.9 g on Day 0 to 45.7+/-1.2g on Day 12 (P<0.05 compared to vehicle-treated mice). In db/db mice, after treatment with same dose of the extract, fasting blood glucose levels also decreased significantly from Day 0 of 247+/-13.9 mg/dl to Day 5 of 172+/-7.5mg/dl and to Day 12 of 190+/-2.7 mg/dl (both P<0.01 compared to vehicle-treated group from Day 0 of 239+/-12.1mg/dl to Day 5 of 230+/-8.5mg/dl and Day 12 of 247+/-18.9 mg/dl, respectively). After 12 days of extract treatment, body weight in db/db mice reduced from 61.8+/-1.4 g on Day 0 to 59.8+/-1.1g on Day 12 (P<0.05). Our results support an in vivo anti-hyperglycemic and body weight reduction activity of G. yunnanense extract that may prove to be of clinical importance in improving the management of type 2 diabetes.