Background: Intestinal adaptation following massive intestinal resection requiresnutrient stimulation. However, the relative effects of direct mucosal stimulation by nutrients, the additive effects of biliary-pancreatic secretions, and induced enteric hormones are not known. To investigate this, we compared the alimentary limb and the common limb of a Gastric Roux Y bypass model (GRYB) to each other and to sham operated controls. Methods: Male rats (350 to 400 g) underwent sham and Gastric Roux en Y surgery: (n=8/group). Animals were pair fed and followed for 14 days. Weight and postprandial systemic insulin, leptin, Glucagon-like peptide 2 (GLP-2) and (PYY) levels were quantified. Adaptation was quantified by intestinal gross and microscopic morphology and crypt proliferation in each intestinal limb of the bypass and the equivalent points in the sham intestineResults: Control animals maintained weight, while bypass animals lost weight and exhibited significant adaptive changes with increased bowel width, Villus height, crypt depth and proliferation were increased in both the proximal alimentary limb and the distal common limb. GRYB animals had elevated systemic postprandial PYY and GLP-2 levels. Within the GRYB animals, the proximal alimentary limb had a greater increase in crypt depth than the distal common limb. (All comparisons p<0.05) Conclusions: Despite the significant increase in systemic PYY and GLP-2 levels in the GRYB animals, small bowel adaptation only occurred in bowel segments stimulated by nutrients; there was no additional effect from biliary-pancreatic secretions. Further studies to examine the local factors which mediate the nutrient induced adaptation response are indicated; such local factors could be useful therapy for patients with short bowel syndrome.