Intestinal nutrient infusions result in variable decreases in food intake and body weight based on the nutrient type and the specific intestinal infusion site. We previously found that intrajejunal infusions of a fatty acid and glucose, but not casein hydrolysate, decreases food intake and body weight in lean chow-fed laboratory rats. To test whether obese, high fat-fed animals would show similar decreases in food intake and body weight in response to intrajejunal infusions of the same nutrients, equal kilocalorie loads of these nutrients (11.4 kcal) or vehicle were infused into the jejunum of obese, high fat-fed male Sprague-Dawley rats over 7 h/day for 5 consecutive days. Food intake was continuously monitored and body weight was measured daily. After the infusion on the final day, rats were sacrificed and plasma collected. Similar to lean chow-fed rats, intrajejunal infusions of LA and Glu, but not Cas, suppressed food intake with no compensatory increase in food intake after the infusion period. In contrast to lean chow-fed rat, only the LA, and not the Glu or Cas, produced decreases in body weight in the obese high fat fed rat. There also were no differences in plasma GLP-1 levels in any of the nutrient infusion groups compared to saline infusion. These results suggest that there is a differential response to the same nutrients in lean versus obese animals.