Abstract: 【Abstract】 Objective To explore the mechanism of Panax notoginseng saponins (PNS) on diabetes treatment and mass loss in KK-Ay mice with genetic type 2 diabetes mellitus (DM), and to identify the main hypoglycemic ingredients. Methods C57 and KK-Ay DM mice were divided into eight groups each comprising six mice: healthy normal, DM model, and DM model treated with PNS (200 mg/kg body mass), ginsenoside Re (Re, 14 mg/kg body mass), ginsenoside Rd (Rd, 15 mg/kg body mass), ginsenoside Rg1 (Rg1, 40 mg/kg body mass), ginsenoside Rb1 (Rb1, 60 mg/kg body mass) and notoginsenoside R1 (R1, 6 mg/kg body mass). The PNS were intraperitoneal injection administered for 30 d, while the Re, RB1, Rg1, Rd and Re were intraperitoneal injection administered for 12 d. The fasting blood sugar (FBG), glucose tolerance (GT), serum insulin, leptin, body weight, food consumption, and levels of adipose tissue and blood lipid were determined. Results On 12 d, lower FBG levels were found in the PNS and Rb1 treated mice compared with the model mice (P<0.05). No statistical differences in FBG levels were found between the rest of the treatment groups and the model group (P＞0.05). After 30 d continuous administration of PNS, the FBG level of the mice further declined (P <0.01). Meanwhile, the serum insulin (P <0.05) and insulin resistance index (P <0.01) of the PNS treated mice also declined significantly. Compared with model group, the PNS group had lower levels of body weight growth, food consumption, adipose tissue, and leptin (P<0.05). Lower FBG level was also found in Rb1 treated mice (12 d of administration), P<0.05. Conclusion PNS has anti-hyperglycemic and anti-obesity activities by improving insulin and leptin sensitivities in KK-Ay mice. Rb1 may be the hypoglycemic ingredient in the PNS extract.