IL-10 plays a critical role in the induction of specific T-cell tolerance. To date, whether IL-10 induction by antigen application is dose- or time-dependent remains unclear. In this study, IL-10 induction by allergen exposure was investigated in the several schedules. Oxazolone was repeatedly applied to mouse ear, and mRNA of inflammatory cytokines in lesional skins was measured. The results indicated that continuous high-dose antigen exposure induces IL-4 as well as abundant IL-10 production. Monocytes/dendritic cells and T cells are major source of IL-10. Allergen-specific immunotherapy is resumed before antigen scattering: preseason. We evaluated safe-loading dose of allergens in preseasonal therapy focusing Tr1 induction. Restarting immunotherapy with high dose effectively augmented IL-10 expression accompanied with further induction of IL-4 and inflammatory cytokines. Therefore, the protocol restarting with low-dose antigen is preferential to obviate the risk of exacerbation or anaphylaxis.