It has been shown that in contrast to peripheral fat, visceral fat is an important risk factor for cardiovascular diseases and diabetes. In this study, we investigated whether dexfenfluramine (dF), a compound known to decrease body fat, affects fat mass differentially in various regions of the body. We used a moderately obese rat model fed a high-fat diet (40% fat). After 35 days on the diet, rats were divided into three groups: a dF-treated group ([D]2.5 mg/kg intraperitoneally twice daily), a pair-fed group (Cp), and a control group (C) fed ad libitum. C and Cp rats were injected with saline. After 4 weeks of treatment, body fat, fat cell morphology, and metabolism were determined in subcutaneous (inguinal [ING]) and visceral (retroperitoneal [RET] and mesenteric [MES]) fat tissues. Food intake in D and Cp rats was similar, and was lower than in the C group. In comparison to Cp and C rats, D rats had lower body weight and body fat, smaller ING and RET fat pad weights, and smaller fat cell size in all depots. No significant differences were observed in fat mobilization between groups; however, fat accumulation tended to be lower in D rats. These data suggest that dF has an effect on adipose tissue independent of its effect on food intake. However, this effect seems to occur without regional specificity.