In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs) from small intestine of transgenic (TGN) DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well-preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8+ and CD4+ T-cell subsets. Administration of OVA via oral + i.p. increased the frequency of CD103+ cells in CD4+ T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8a+ and CD8β+ T-cell subsets in IELs of BALB/c mice. The frequency of Foxp3+ cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25+ subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-β, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa.