A rat model replicating gastric bypass with Roux-en-Y (GB) as used in morbidly obese patients, evolved in our laboratory in stages, using the Zucker rat as an obese model (GB) is presented. In the final model, a 20% gastric fundic pouch to limit the gastric reservoir was created using two staple lines (Ethicon). A 4- to 5-mm end-to-side gastrojejunostomy and a 6- to 8-mm jejunojejunostomy, at 10 cm length of the Roux-en-Y limb, placed 16 cm below the ligament of Treitz, was hand sewn to create a limited area of nutrient digestion and absorption. Controls underwent sham operation. Rats were divided into: (i) sham-op ad lib-fed (Control); (ii) GB; and (iii) sham-op pair fed (PF) in two experiments. In Experiment 1, 24 Zuckers (control n = 8; GB n = 8; PF n = 8) were studied to assess the effectiveness of the model for weight loss. In Experiment 2, 24 Zuckers (8/group) were studied to confirm the effects of the operation on weight loss and on metabolic parameters. Boost was given for 4 days starting 24 h postop and then ground chow was given. Daily food intake (FI), meal size (MZ), meal number (MN), and body weight (BW) were measured. Rats were sacrificed on Day 20 in Experiment 1 and on Day 10 in Experiment 2. Serum metabolites and body fat weight were measured. Data were evaluated using Student's t test. Controls steadily gained BW (5.2-6.1 g/day), reaching approximately 500 g. In GB: FI, MZ, MN, BW, glucose, free fatty acids, insulin, and body fat decreased (P < 0.05). In PF: BW, insulin, triglycerides, and body fat decreased. A dependable, reproducible gastric bypass with Roux-en-Y obesity model was developed. This permits the study of biochemical and eventually molecular mechanism(s) of weight loss resulting from the operation.