The skin plays a critical role in maintenance of water homeostasis. Dysfunction of the skin barrier causes not only delayed wound healing and hypertrophic scarring, but it also contributes to the development of various skin diseases. Dermatitis is a chronic inflammatory skin disorder that has several different subtypes. Skin of contact dermatitis and atopic dermatitis (AD) show epidermal barrier dysfunction. Naxis a sodium channel that regulates inflammatory gene expression in response to perturbation of barrier function of the skin. We found that in vivo knockdown of Naxusing RNAi reduced hyperkeratosis and keratinocyte hyperproliferation in rabbit ear dermatitic skin. Increased infiltration of inflammatory cells (mast cells, eosinophils, T cells, and macrophages), a characteristic of dermatitis, was reduced by Naxknockdown. Upregulation of PAR-2 and thymic stromal lymphopoietin (TSLP), which induce Th2-mediated allergic responses, was inhibited by Naxknockdown. In addition, expression of COX-2, IL-1β, IL-8, and S100A9, which are downstream genes of Naxand are involved in dermatitis pathogenesis, were also decreased by Naxknockdown. Our data show that knockdown of Naxrelieved dermatitis symptoms in vivo and indicate that Naxis a novel therapeutic target for dermatitis, which currently has limited therapeutic options.