This study aimed to determine the relative efficacy of the macronutrients, protein, fat and carbohydrate to induce satiation and satiety in rats in relation to macronutrient activation of neurons in the nucleus of the solitary tract (NTS). Male Sprague Dawley rats were schedule-fed twice a day for 2h, receiving 100% of daily ad-libitum energy intake. On test day 1, 30min before the first scheduled meal of the day, rats were gavaged with an 8kcal isocaloric, isovolumetric solution of a glucose, lipid or peptone macronutrient solution or a non-caloric saline solution. To assess satiation, thirty minutes later rats were given access to food for 2h and food intake determined. A second 2h food access period 3h later was used for assessment of satiety. On the second test day, rats were gavaged as before and killed 90min after food presentation. Blood was collected for measurement of circulating metabolic markers. Brains were removed for analysis of c-Fos expression by in situ hybridization in the NTS.Rats which received saline consumed a similar amount of food compared to pre-gavage intakes.However, rats gavaged with a caloric macronutrient solution all reduced food intake by 18-20kcal. Interestingly, the reduction in caloric intake was greater than the caloric value of the macronutrient solution gavaged and was sustained following the second scheduled meal. Quantification by in situ hybridization of c-Fos mRNA expression in the NTS 90 minutes post-gavage, showed a significant increase with each macronutrient, but was 24-29% higher with a lipid or peptone gavage compared to a glucose gavage. In conclusion, when delivered directly to the stomach, all macronutrients can be equally effective in inducing satiation with significant neuronal activation in the NTS of the hindbrain.