AbstractObjective: We examined the effectiveness of sibutramine to modulate food intake and body composition in rats with two levels of adiposity imposed by the duration of their maintenance on a moderate‐fat diet.Research Methods and Procedures: Male Sprague–Dawley rats were fed a 32% fat diet from weaning until 2 or 4 months of age, at which point, body fat was either 15% or 25%, respectively, as measured by DXA. Sibutramine (0.6 or 2 mg/kg, orally) was then given daily for 2 weeks.Results: Food intake and body weight decreased acutely in a dose‐related manner in both groups with sibutramine treatment. In all rats, food intake suppression was attenuated after multiple days of sibutramine. Both 15%‐ and 25%‐fat rats had a persistent decrease in weight gain over the 2‐week period in response to sibutramine. The older, 25%‐fat rats were more sensitive to sibutramine than the younger, 15%‐fat rats with regard to the magnitude of overall food intake inhibition, decrease in body weight gain, and caloric efficiency. Despite these differences, sibutramine produced the same relative reductions in fat mass and had no effect on lean mass in the two groups.Discussion: Thus, sibutramine produced equivalent efficacy on carcass fat loss in both groups, despite less inhibition of feeding and body weight gain in leaner rats. Whether these changes are a result of the leaner rats being younger and on a steeper growth curve compared with older, fatter rats or whether this is a direct function of their level of adiposity remains to be determined.