Objective To establish a mouse model of intestinal allergy by epicutaneous sensitization (ES).Methods After comparing the degree of intestinal allergy induced by ES (on the ear or back skin) or intraperitonealinjection, the method of ES (on ear skin) with higher sensitivity and easier operation was selected. Calcipotriol ointmentwas used for induction of the inflammation of mice ear skin. At the same time, mice were epicutaneously sensitized withovalbumin (OVA) for two weeks. The established model was evaluated according to the below symptoms, includingintestinal allergic symptoms, jejunal capillary permeability, plasma tIgE and mMCP-1 levels, and jejunal histopathologicalchanges after OVA challenge (i.g.). Results In contrast to intraperitoneal injection, the ES induced higher production ofplasma tIgE and mMCP-1. Moreover, the mice in the model group showed obvious intestinal allergy symptoms, such asrapid scratching, arching back and diarrhea, hypothermia (the rectal temperature was decreased about 1. 2℃), increasedjejunal capillary permeability (about 2 times), and robustly increased plasma tIgE and mMCP-1 levels. Histologicalchanges were also observed, such as the damage of jejunum mucosa, infiltration of inflammatory cells and the increase ofmast cells (about 5 times). Conclusions The established mouse model not only has typical pathological characteristics offood allergy, but also represents the sensitization pathway of skin exposure to allergens. It may also provide a new research tool for further mechanism research and the prevention/ treatment of food allergy.