The present study was undertaken in order to evaluate the possible mechanisms of action involved in the hypoglycaemic activity of the aqueous extract of Chamaemelum nobile (CN) (20 mg kg
−1). This study was carried out in Multi Low-Dose Streptozotocin-induced (MLDS) diabetic mice. Hypoglycaemic effect of CN was studied after both single and repeated oral administration of CN aqueous extract (20 mg kg). Endogenous glucose production was estimated using primedcontinuous 3-3 H glucose infusion technique. While, euglycemic hyperinsulinemic glucose clamp technique was used to assess peripheral insulin sensitivity. Both single and repeated oral administration (s) of aqueous CN extract evoked a prominent hypoglycaemic activity in MLDS diabetic mice. In other hand, 3-3 H glucose infusion demonstrated that this hypoglycaemic activity was accompanied by a decrease in basal endogenous glucose production (EGP). EGP was lower in CS-treated group when compared to the control group, 15.5±0.5 vs 27.2±7.1 mg kg −1 min −1 (p<0.001) respectively. While, the metabolic clearance rate of glucose remains unchanged. In addition, we have demonstrated that CN treatment also improves insulin sensitivity in peripheral tissues, suggested by the observed higher levels of the glucose infusion rate. We can conclude that inhibition of basal endogenous glucose production and amelioration of insulin sensitivity in peripheral tissues account for the hypoglycaemic activity of aqueous CN extract in MLDS diabetic mice.