Objective: To investgate the role of Toll-like receptor(TLR) 2 and TLR4 in pathogenesis of atopic dermatitis(AD) and the effect of topical tacrolimus ointment on expression of TLR2 and TLR4 in lesional AD skin.Methods: Immunohistochemistry was employed to study the expression of TLR2 and TLR4 in normal skin and lesional AD skin before and after using topical tacrolimus ointment.Results: The basal keratinocytes in normal skin constitutively expressed TLR2 and TLR4. In contrast,lesional epidermis from 9 patients with acute AD overexpressed TLR2 and TLR4 on the whole epidermis keratinocytes with membranous and cytoplasmic staining pattern.After using topical tacrolimus ointment for three weeks,TLR2 and TLR4 were expressed on basal and suprabasal keratinocytes with membranous and cytoplasmic staining pattern.Conclusion: These data suggest that TLR2 and TLR4 expressed by epidermal keratinocytes constitute part of the innate immune system of the skin,and increased TLR2 and TLR4 expression may be related to the skin innate immuno-inflammatory response in atopic dermatitis.Topical tacrolimus may directly or indirectly inhibit or downregulate TLR2 and TLR4 expression in KC and inhibit skin innate immuno-inflammatory response related to TLR-NF?B signal transduction and regulation in atopic dermatitis.