Objective:To examine the effects of Sapium ellipticum(SE) leaf extract on the hepatic activities of glucokinase and glucose-6-phosphatase in streptozotocin-induced diabetic Wistar rats.Methods:STZ-induced diabetic Wistar rats(four groups,n = 8) were used in this study.SE was assessed at two different doses,400 and 800 mg/kg BW,in comparison with metformin(METF)(12 mg/kg BW) as a reference antidiabetic drug.All treatments were done orally(p.o),twice daily at 8 h interval for a period of 21 days.Glucokinase and glucose-6-phosphatase activities were respectively determined using standard protocols.Hepatic and muscle glycogen contents were estimated as well.Results:STZ caused significant decrease in glucose-6-phosphatase activity and concomitant increase in glucokinase activity.SE extract especially at 400 mg dosage significantly reversed the alterations by increasing glucokinase activity by 40.31% and inhibiting glucose-6-phosphatase activity by 37.29% compared to diabetic control animals.However,the effects were significantly lower than that of METF which enhanced glucokinase activity by94.76% and simultaneously inhibited glucose-6-phosphatase activity by 49.15%.The extract also improved hepatic glycogen level by 32.37 and 27.06% at 400 and 800 mg dosage respectively.HPLC-MS analysis of some SE fractions in dynamic MRM mode(using the optimized compound-specific parameters) revealed among other active compounds,the presence of amentoflavone,which has been associated with antidiabetic function.Conclusions:The ability of SE extract to concurrently inhibit glucose-6-phosphatase and activate glucokinase in this study suggests that it may be a treatment option for type 2 diabetes patients,and the presence of amentoflavone in the plant extract may account for its anti-diabetic potential. Objective: To examine the effects of Sapium ellipticum (SE) leaf extract on the hepatic activities of glucokinase and glucose-6-phosphatase in streptozotocin-induced diabetic Wistar rats. Methods: STZ-induced diabetic Wistar rats (four groups, n = 8) were used in this study. SE was assessed at two different doses, 400 and 800 mg / kg BW, in comparison with metformin (METF) (12 mg / kg BW) as a reference antidiabetic drug. , twice daily at 8 h interval for a period of 21 days. Glucokinase and glucose-6-phosphatase activities were determined by standard protocols. Hepatology and muscle glycogen contents were estimated as well. Results: STZ caused significant decrease in glucose-6- phosphatase activity and concomitant increase in glucokinase activity. SE extract especially at 400 mg dose diluted physically alter protein by glucokinase activity by 40.31% and inhibiting glucose-6-phosphatase activity by 37.29% compared to diabetic control animals .However, the effects were significantly lower than that of METF which enhanced glucokinase activity by 94.76% and later inhibited glucose-6-phosphatase activity by 49.15%. The extract also improved hepatic glycogen level by 32.37 and 27.06% at 400 and 800 mg dosage respectively. HPLC-MS analysis of some SE fractions in dynamic MRM mode (using the optimized compound-specific parameters) revealed among other active compounds, the presence of amentoflavone, which has been associated with antidiabetic function. Conlusions: The ability of SE extract to concurrently inhibit glucose-6-phosphatase and activate glucokinase in this study suggests that it may be a treatment option for type 2 diabetes patients, and the presence of a fill oflavone in the plant extract may account for its anti-diabetic potential.