Introduction: Pathologic accumulation and over-activation of mast cells and eosinophils have been implicated in multiple chronic inflammatory diseases in the GI tract including eosinophilic esophagitis, gastritis, gastroenteritis, and colitis. Collectively termed eosinophilic gastrointestinal disorders (EGIDs), these medical conditions lead to reduced quality of life due to debilitating symptoms such as dysphagia, abdominal pain, nausea, vomiting and diarrhea. Current treatment options for EGIDs have limited efficacy, significant side effects, and are often inappropriate for chronic use. Siglec-8 is an inhibitory receptor selectively expressed on human eosinophils (eos) and mast cells (MCs). Preclinical studies have demonstrated that anti-Siglec-8 monoclonal antibodies (mAbs) can deplete blood and tissue eosinophils and inhibit mast cell activity. This study examines the activity of an anti-Siglec-8 mAb in a mouse eosinophilic gastroenteritis (EGE) model.