1. The intestine has been implicated as a site of increased glucose utilization by the antihyperglycaemic drug, metformin. This study makes a quantitative assessment of this effect. 2. Glucose utilization by the intestine and hind limb region was determined by arterial-venous glucose difference adjusted for blood flow rate in fasted rats receiving a hyperglycaemic hyperinsulinaemic infusion. 3. Intrajejunal administration of metformin, 250 mg kg-1, increased glucose disposal during the infusion procedure, associated with increased glucose utilization in the intestine by 69% and in the hind limb region by 40%. 4. Metformin, 250 mg kg-1, increased glucose disappearance during an intravenous glucose tolerance test. This was accompanied by increased uptake of tritiated 2-deoxy-D-glucose into the intestinal mucosa to a greater extent than into skeletal muscles (per unit wet weight of tissue). 5. The results demonstrate that the intestinal mucosa is a quantitatively important site of increased glucose utilization during the blood glucose-lowering effect of metformin.