Intraperitoneal (IP) fat accumulation in humans is a risk factor for a number of diseases. We tried to increase this particular adipose mass in rats by long-term administration of low-dose dexamethasone (Dex) and/or elimination of other fat depots. Male adult Wistar rats were lipectomized (Lip) or sham-operated (Sh). Bilateral lipectomy of retroperitoneal and inguinal fat pads was performed under anesthesia with Na pentobarbital 40 mg/kg supplemented with ether. After 8 days, half the animals of each group received Dex in their drinking water (0.1 microgram/mL) while the other half received water (W), for a total of four groups: Sh-W, Lip-W, Sh-Dex, and Lip-Dex. Body weight (BW) and food and water intake were measured throughout the treatment period. A glucose tolerance test was performed 34 days after starting Dex treatment, and then rats were killed, fat depots were weighed, and plasma and liver were obtained for metabolic determinations. Dex rats ate the same amount of food as W controls, but gained significantly less weight (2.02 +/- 0.18 v 3.82 +/- 0.10 g/d, P < .01). Mean daily W intake was approximately 40 mL/d in all groups, which means that Dex rats ingested approximately 4 micrograms/d Dex. Average glycemic values during the 180-minute glucose tolerance test were as follows: Sh-W, 162 +/- 13; Lip-W, 166 +/- 7; Sh-Dex, 118 +/- 6; and Lip-Dex, 229 +/- 27 mg/dL. These values show that glucose tolerance was improved by Dex treatment alone, but was impaired in Lip-Dex animals. The same trend was evident for the relative weights (percent of BW) of two intact adipose depots: IP and epididymal (EPI) (Sh-W, 2.08 +/- 0.13 and 1.35 +/- 0.11, respectively; Lip-W, 1.67 +/- 0.15 and 1.17 +/- 0.11; Sh-Dex, 1.66 +/- 0.10 and 1.28 +/- 0.07; Lip-Dex, 2.41 +/- 0.11 and 1.53 +/- 0.09). Average glycemia for all rats was significantly correlated with IP (r = .55, P < .01) but not with EPI; moreover it was correlated in the Sh-W control group (r = .81, P < .05), suggesting a normal relation between these variables. Liver triglycerides (LTG), which were elevated in Dex rats, were also correlated with IP (r = .51, P < .02 for all rats and r = .82, P < .05 for Sh-W rats). The results show that long-term administration of low-dose Dex has some different effects in normal versus Lip rats concerning mainly the IP fat depot, the relative mass of which seems to significantly affect glucose tolerance.