To explore the hypoglycemic effect of Moringa oleifera leaf polysaccharide(MOLP)on diabetic mice and its corresponding mechanism,a streptozotocin(STZ)-induced diabetic mouse was modeled.The mice were then divided into groups exposed to low(100 mg/kg·bw),medium(200 mg/kg·bw),and high dosage(400 mg/kg·bw)of MOLP,with a normal blank group,model group and a positive drug group(hydrochloric acid dimethylbiguanide,200 mg/kg·bw).Eight mice in each group were gavaged for 28 d.Fasting blood glucose,serum glycated protein,serum insulin,hepatic/myocardial glycogen and other biochemical indexes were determined.Additionally,the key genes of glucose metabolism,including liver X receptor(LXR),pancreatic-duodenal homeobox-1(PDX-1),glucokinase(GK),phosphoenolpyruvate carboxykinase(PEPCK),glucose 6-phosphatase(G6Pase),glucose transporter type 2(GLUT2)and insulin receptor substrate 1/2(IRS1/2)were measured in the liver and the pancreas.Furthermore,the mice's liver and pancreas tissues in each group were stained with HE to observe their histomorphology.The results showed that MOLP exhibited a significant hypoglycemic effect and a dose-response relationship.The level of blood glucose reduction in the MOLP high-dose group(400 mg/kg·bw)was closest to that of the positive drug group.The underlying mechanism was that the significantly upregulated expression of LXR and PDX-1 ameliorated the glucose metabolism disorders in diabetic mice by regulating the expression of their downstream genes including PEPCK,G6Pase,GK,GLUT2 and IRS1/2 mRNA.This regulation facilitated the improvement of the damaged liver and pancreatic tissues,increased serum insulin and hepatic glycogen content and ultimately resulted in a hypoglycemic effect.