A one year old castrated male Boxer Dog presented to the Cornell University Hospital for Animals (CUHA) Internal Medicine Service for evaluation of chronic diarrhea of eight months duration. Since that time, the patient has had diarrhea characterized by hematochezia, mucus, tenesmus and increased frequency. The dog has also been losing weight despite a voracious appetite. According to the owner, no diagnostics were performed at the referring veterinarian and empirical treatment with two courses of a dewormer and a diet change were ineffective. Physical examination was unremarkable with the exception of a low body condition score of 2/9, and a painful rectal exam with brown soft feces and frank blood. Fecal floatation and baseline blood work were normal apart from mild changes attributed to inflammation. The primary differential diagnosis at this point was colitis. A colonoscopy was performed which revealed a diffusely thickened and ulcerated mucosa. Endoscopic biopsies were submitted for histopathology, gram stain, PAS (Periodic Acid-Schiff) staining, FISH (Fluorescence In-Situ Hybridization) analysis and culture for Campylocacter, Salmonella, and Escherichia coli. Histopathology was characterized by marked loss of glands and infiltration of neutrophils and PAS-positive macrophages. FISH analysis showed multifocal clusters of invasive E. coli. These findings are consistent with a diagnosis of granulomatous colitis of Boxer dogs. Treatment was initiated with enrofloxacin and continued on the basis of sensitivity testing of E. coli.