Most crucial role of epidermis is to maintain efficient barrier between the organism and its environment. This barrier is however perturbed in inflammatory skin conditions like atopic dermatitis (AD), one common chronic disease. This review depicts characteristics of a model intending to reproduce epidermal features of AD in vitro. Firstly, methyl-β-cyclodextrin (MβCD) during reconstruction of epidermis was used to deplete cholesterol from plasma membrane because this condition reproduces characteristics of AD at transcriptomic level in monolayer cultures. Major changes are confirmed after same treatment inside reconstructed human epidermis (RHE). However, since early treatment do not reveal impairment to reconstruct a functional epidermal barrier and given the importance of the Th2 dysregulated immune response in AD, cholesterol-depleted RHE at day 11 of reconstruction were then incubated with three Th2-related cytokines (IL-4, IL-13 and IL-25) previously reported as playing important roles in the development of AD, as well as altering overall function of epidermal barrier. When combining both treatments, essential epidermal features of AD are observed. Indeed, RHE then exhibit spongiosis, disappearing granular layer, alteration of barrier function, as well as dysregulated expression levels for genes involved in AD pathogenesis. Moreover, while trying to identify individual roles for each component used to create AD-like alterations, incubation with IL-4 following cholesterol depletion from plasma membrane was found inducing most of the reported alterations. This model suggests potential for better investigations of epidermal AD features and may be considered for eventual in vitro screening of cosmetics or therapeutic compounds.