Continuous subcutaneous administration of leptin normalizes blood glucose levels in rodent models of type 1 and type 2 diabetes independent of changes in food intake, body weight and plasma insulin. We tested whether an acute intravenous leptin infusion changed blood glucose in normal and diet-induced leptin resistant rats to determine if this measure could be used as a marker of leptin sensitivity. Leptin responsive chow fed rats and diet induced leptin resistant Male Sprague Dawley rats were fitted with thoracic jugular vein catheters. Four days after surgery, conscious rats were infused intravenously (i.v) with either saline for 32 minutes, low dose (LD) leptin (1.9µg/kg/min) followed by high dose (HD) leptin (3.8µg/kg/min) for 16 minutes each, or only HD leptin for 16 minutes. There was no change in blood glucose after an acute i.v infusion of either LD leptin or HD leptin alone for 16 minutes. An i.v. infusion of LD followed by HD leptin for 16 minutes each, significantly decreased serum glucose in leptin responsive rats but not in leptin resistant rats. Leptin infusions increased serum leptin in all rat groups, but had no effect on plasma glucagon or 12 hour weight gain and energy intake in any group of rats. These results show that leptin has an acute glucose lowering effect that reflects the leptin responsiveness of the rat. This effect is consistent across controls and different leptin resistant rat models and the acute, non-lethal test provides a novel method of testing leptin responsiveness in rats.