Background and PurposeAtopic dermatitis (AD) is a multifactorial skin condition with complex interactions of innate and adaptive immune responses. There are several existing therapies for AD, including topical glucocorticosteroids, emollients, phototherapies, calcineurin inhibitors and immunosuppressants, such as cyclosporine A. Although these therapies reduce inflammation, they also cause serious side effects. Therefore, it is necessary to develop new therapeutic approaches for AD treatment without side effects. There are several studies on natural materials or toxins, such as herbs, ginseng extract and snake venom, for AD treatment. However, treatment of AD with bee venom and its major component, melittin has rarely been studied.Experimental ApproachEffects of bee venom and melittin were studied in a model of AD in vivo induced by 1‐chloro‐2,4‐dinitrobenzene (DNCB) in female Balb/c mice and in cultures of human keratinocytes, stimulated by TNF‐α/IFN‐γ. The potential pharmacological effects of bee venom and melittin on these in vivo and in vitro AD‐like skin disease models were studied.Key ResultsBee venom and melittin exhibited potent anti‐atopic activities, shown by decreased AD‐like skin lesions, induced by DNCB in mice. In vitro studies using TNF‐α/IFN‐γ‐stimulated human keratinocytes showed that bee venom and melittin inhibited the increased expression of chemokines, such as CCL17 and CCL22, and pro‐inflammatory cytokines, including IL‐1β, IL‐6 and IFN‐γ, through the blockade of the NF‐κB and STAT signalling pathways.Conclusions and ImplicationsOur results suggest that bee venom and melittin would be suitable for epicutaneous application, as topical administration is often appropriate for the treatment of AD.