Abstract L-selectin is a cell adhesion molecule that plays an important role in leukocyte migration especially to peripheral lymph nodes. L-selectin deficiency is known to decrease subcutaneous immune responses, however, the role of L-selectin in atopic dermatitis model is unknown. Moreover, it is not clear on which cell subset the expression of L-selectin is critical for cutaneous inflammation. Here, we showed that in mouse atopic dermatitis model elicited by epicutaneous sensitization with ovalbumin (OVA) OVA-specific antibody production and dermatitis is completely lost with L-selectin deficiency. We also found that L-selectin expression on CD4+ T cells is critical for antibody production, whereas L-selectin expression on both CD4+ and CD8+ T cells is important for dermatitis. Moreover, as few as 100 OVA-specific CD4+ T cells were able to elicit OVA-specific antibody production in L-selectin deficient mice. When wild-type CD4+ T cells were intravenously injected to L-selectin deficient mice, OVA-specific antibody-forming cells existed mostly in draining lymph nodes, suggesting that L-selectin-positive CD4+ T cells recruited to draining lymph nodes could muster antibody-forming cells independent of L-selectin. These results suggested that this mouse atopic dermatitis model is completely L-selectin dependent with L-selectin on CD4+ T cells and CD8+ T cells playing distinctive roles, and targeting L-selectin may be an option for treating atopic dermatitis.