This study examined biopsies from 12 dogs diagnosed with chronic inflammatory enteropathy (CIE) to quantify expression of the GI receptor for advanced glycation end products (RAGE), a pattern recognition receptor of the innate immune system. These biopsies were compared with expression from biopsies of 9 healthy dogs. Epithelial RAGE expression in the duodenum, ileum, and colon was higher in dogs with CIE, and several histologic and inflammatory lesion criteria as well as markers of inflammation (ie, serum C-reactive protein, fecal calprotectin concentration) were related to epithelial RAGE expression in these intestinal structures. These findings suggest that transmembrane RAGE expression and intracellular RAGE signaling are involved in the chronic inflammatory response of dogs with CIE. RAGE antagonization may present a novel therapeutic intervention for chronic GI inflammation.