MINI-ABSTRACT We performed bile diversions matching the modified biliary flow occurring after gastric bypass (GBP) in rats. Our results strongly suggest that the only modification of bile routing mimics the main metabolic benefits of GBP: 1) improved glucose control, 2) decreased food intake because of disinterest in high calorie food. STRUCTURED ABSTRACT Objective: To evaluate the role of bile routing modification on the beneficial effects of gastric bypass surgery on glucose and energy metabolism. Summary background data: Gastric bypass surgery (GBP) promotes early improvements in glucose and energy homeostasis in obese diabetic patients. A suggested mechanism associates a decrease in hepatic glucose production (HGP) to an enhanced intestinal gluconeogenesis (IGN). Moreover, plasma bile acids are elevated after GBP and bile acids are inhibitors of gluconeogenesis. Methods: In male Sprague-Dawley rats, we performed bile diversions from the bile duct to the midjejunum or the mid-ileum to match the modified bile delivery in the gut occurring in GBP. Body weight, food intake, glucose tolerance, insulin sensitivity and food preference were analyzed. The expression of gluconeogenesis genes was evaluated in both the liver and the intestine. Results: Bile diversions mimicking GBP promote an increase in plasma bile acids and a marked improvement in glucose control. Bile bioavailability modification is causal since a bile acid sequestrant suppresses the beneficial effects of bile diversions on glucose control. In agreement with the inhibitory role of bile acids on gluconeogenesis, bile diversions promote a blunting in HGP, whereas IGN is increased in the gut segments devoid of bile. In rats fed a high fat-high sucrose diet, bile diversions improve glucose control and dramatically decrease food intake due to an acquired disinterest in fatty food. Conclusion: This study shows that bile routing modification is a key mechanistic feature in the beneficial outcomes of GBP.