Glucagon like peptide 1, an intestinal hormone that plays an important role in glucose metabolism, is released from mucosal L-cells following nutrient ingestion and contributes to the incretin effect (enhancement of insulin secretion resulting from enteral versus intravenous glucose administration). Mechanisms linking nutrient absorption and GLP-1 secretion are unknown; studies addressing this have been hampered by relatively low concentrations of GLP-1 in the circulation, particularly in small animal models. We hypothesized that GLP-1 levels are higher in intestinal lymph than plasma, and provide a novel system in which to study meal-induced hormone secretion. We addressed this hypothesis in conscious rats with indwelling portal vein and distal intestinal lymph duct catheters. Plasma and lymph were sampled before and for 240 minutes after instillation of a liquid meal into the gastrointestinal tract. Lymph concentrations of glucose, insulin, and GLP-1 were assayed. Before and after the Ensure feeding, portal plasma insulin levels were approximately twice those found in intestinal lymph. Contrastingly, GLP-1 levels were 5-6 times higher in lymph than portal plasma following nutrient administration (and even higher compared to peripheral circulation), and these levels dramatically exceeded the ratio of lymph:plasma PYY concentrations. This is the first observation of a GI hormone being disproportionately transported into lymph. Remarkable levels of GLP-1 in intestinal lymph suggest lymphatic sampling as a more sensitive means of studying GLP-1 secretion in vivo. Additionally, the possibility is raised that intestinal lymph may serve as a specialized signaling conduit for regulatory peptides secreted by GI endocrine cells.