Obesity affects 30% of the United States population and its detrimental effects are obesity-related metabolic diseases. For patients refractory to conventional weight loss therapy, gastric bypass surgery is one of the proven methods for inducing a sustained weight loss and reversing the metabolic sequelae of obesity. To understand the mechanisms of weight loss and the amelioration of related metabolic comorbid conditions, a reproducible animal model is needed. We report our developmental experience with rat models of sequential Roux-en-Y gastric bypass after reproducing the diet-induced obesity that characterizes the hallmarks of human obesity. Four experiments were performed to induce weight reduction through successive modifications: In Experiment 1 a 20% stapled gastric pouch with a 16 cm biliary-pancreatic limb and a 10 cm alimentary limb accomplished sufficient weight loss within 10 days to ameliorate metabolic changes associated with obesity, but the occurrence of gastrogastric fistulas prevented sustained weight loss; in Experiment 2 the model was improved by dividing the stomach to avoid gastrogastric fistula, but again sustained weight loss was not achieved; in Experiment 3 the biliary-pancreatic limb was lengthened from 16 to 30 cm, reducing the common channel to approximately 18 cm. Sustained weight loss was achieved for 28 days. In Experiment 4 the model in Experiment 3 was modified by dividing the stomach between two rows of staples. Sustained weight loss was observed for 67 days. We developed a reproducible rat model of Roux-en-Y gastric bypass. The existence of this model opens a new field of research in which to study the metabolic sequelae of obesity and the mechanisms of weight loss.