Half of the 3-month-old male Sprague-Dawley rats fed a diet enriched in calories, sucrose and fat (CM diet) for 3 months developed diet-induced obesity (DIO) while the remainder were diet resistant (DR), gaining the same amount of weight as chow-fed controls. DIO was associated with basal hyperinsulinemia and 196 percent heavier retroperitoneal fat pads than DR and chow-fed rats. Intravenous glucose infusion (lg/kg) also produced greater insulin release in DIO rats associated with a 25 percent reduction in glucose disposal rates; areas under the insulin curve were 273 and 51 percent higher than chow-fed and DR rats, respectively. DR rats, on the other hand, showed normal glucose disposal rates but increased insulin release to a glucose load (148 percent greater area under the curve than chow-fed rats). Glucose infusion produced activation of the sympathetic nervous system with release of norepinephrine (NE) into the plasma in chow-fed and DIO but not DR rats which had 40-50 percent lower areas under the NE curve. Also, the areas under the NE curve correlated with body weight gain (r = 0.632; P = 0.040) and retroperitoneal fat pad weight (r = 0.707; P = 0.030) in DR and DIO rats suggesting that glucose-induced sympathetic activation was in some way related to an underlying mechanism of body weight regulation in Sprague-Dawley rats.