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Food allergy is an antigen‐specific immunological adverse reaction after exposure to a given food. Multiple clinical studies showed that oral immunotherapy (OIT) is effective for the prevention and treatment for food allergy that is developed in infants and children. However, the effectiveness of OIT for epicutaneously sensitized food allergy remains unclear. Previously, we established a mouse model of epicutaneous‐sensitized food allergy. In this model, systemic allergic reaction including intestinal and skin symptoms, such as anaphylaxis, was observed. We treated this model with OIT in two ways (OIT before sensitization or OIT during the sensitization phase) and evaluated the preventive effect of both methods. OIT before sensitization significantly ameliorated mast cell degranulation in sensitized skin, but there was no decrease in rectal temperatures or in mast cell degranulation in the jejunum. However, OIT administered during the sensitization phase significantly ameliorated the decrease in rectal temperature and mast cell degranulation in the skin and jejunum. OIT before sensitization increased the regulatory T cells in mesenteric lymph node (MLN), but not in the spleen, and it reduced antigen‐specific IgG, but not IgE, production compared with the non‐OIT control. However, OIT during sensitization caused a greater increase in regulatory T cells in both the MLN and spleen and reduced antigen‐specific IgE and IgG generation compared with the non‐OIT control group. Thus, OIT during the sensitization phase was effective for the prevention of epicutaneous‐sensitized food allergy. [ABSTRACT FROM AUTHOR]