Although several in vivo antigenicity assays using parenteral immunization are operational, no full validated enteral models are available to study food allergy and allergenicity of food proteins. To further validate a developed enteral Brown Norway (BN) rat food allergy model, systemic and local immune-mediated reactions were studied upon oral challenges. The animals were exposed to ovalbumin (OVA) by daily gavage dosing (1 mg OVA/rat/day) for 6 weeks, without the use of an adjuvant, or by intraperitoneal injections with OVA together with AL(OH)3. Subsequently, effects on breathing frequency, blood pressure, and gastrointestinal permeability were investigated upon an oral challenge with 10 to 100 mg OVA in vivo. In both parenterally and orally sensitized rats, an increase in gut permeability (increased passage of beta-lactoglobulin as bystander protein) was determined between 0.5 and 1 h after an oral OVA challenge was given. An oral challenge with OVA did not induce a clear effect on the respiratory system or blood pressure in the majority of the animals. However, some animals demonstrated a temporary decrease in breathing frequency or systolic blood pressure. Upon oral challenge with OVA of orally and parenterally sensitized animals, local effects were observed in all animals whereas systemic effects were observed at a low frequency, which reflects the situation in food allergic patients after an oral challenge. These studies show that the BN rat provides a suitable animal model to study oral sensitization to food proteins as well as immune-mediated effects after oral challenge with food proteins.