Abstract: OBJECTIVE To explore the function of fenugreek seed and mulberry leaf extract(FSML) on regulating the blood glucose level and its related molecular mechanism. METHODS Two rat models of dexamethasone(Model 1) and alloxan(Model 2) were established. The concentration of blood glucose, blood lipids and the protein expression levels of the IRS1, GLUT4 and PPARg were tested to evaluate its hypoglycemic function. RESULTS In the Model 1, the FSML treatment groups at both two doses had a significant lower 0.5 h blood goucose level and AUC value compared to the Model group(P<0.05). In the Model 2, the high dose of FSML treatment group reduced the 0.5 h blood glucose level and AUC value when compared with the model group(P<0.05). The results of the Western blot test showed that two FSML treatments groups significantly increased the GLUT4 and PPARγ protein expression levels when compared with the model group(P<0.05) in Model 1. CONCLUSION This study demonstrates that the FSML has the potential anti-hyperglycemic effect and the possible mechanism is that FSML can regulate the insulin signal pathway through up-regulating the protein expression of PPARγand increase the protein expression of GLUT4, accordingly the cellular blood glucose uptake is increased and the insulin resistance in the muscular and adipocyte tissues is decreased.