A six year old Paint mare was evaluated for acute colic that was unresponsive to analgesics. Pertinent historical facts at the time of evaluation included intermittent colic episodes and weight loss in the few months prior to presentation, skin lesions, and manure of a soft consistency. Based upon physical examination, a surgical exploration was performed and revealed multiple, circumferential mural bands and dozens of raised, red, serosal plaques throughout the length of the small intestine. Biopsies obtained from both the affected intestine and skin revealed a massive, transmural infiltration of eosinophils with lesser numbers of lymphocytes, macrophages, and plasma cells. These findings confirmed a diagnosis of multi-systemic eosinophilic epitheliotropic disease, an uncommon disorder in the horse. This paper will describe the clinical features, diagnosis, prognosis, and treatment options for a horse with multi-systemic eosinophilic epitheliotropic disease.