Tapinarof is a non-steroidal, small molecule aryl hydrocarbon receptor (AhR) agonist that is being developed for the treatment of atopic dermatitis (AD). AD is a chronic inflammatory skin disease mediated by type 2 helper T (Th2) cells, characterized by impaired epidermal differentiation and skin barrier function. Tapinarof has been reported to regulate target gene expression through activation of AhR, improve skin barrier function, and exhibit an antioxidant effect. In this study, we investigated the pharmacological properties of tapinarof and its efficacy in mice with AD-like skin inflammation induced by 2, 4-dinitrofluorobenzene (DNFB). Tapinarof induced the mRNA expression of CYP1A1, an indicator of AhR activation, induced the mRNA expression of NAD(P)H: quinone oxidoreductase (NQO1), an antioxidant enzyme in human peripheral blood mononuclear cells (PBMCs) stimulated with T-cell activators. It also suppressed the production of interleukin (IL)-4, a Th2 cytokine. In mice with AD-like dermatitis, topical administration of tapinarof promoted the expression of Cyp1a1 and Nqo1 in the skin. It suppressed IL-4 production, the ear swelling, and histopathological changes. Tapinarof also suppressed an increase in transepidermal water loss (TEWL), an indicator of skin barrier function. These results indicate that tapinarof suppresses AD-like skin dermatitis and suggest that a variety of pharmacological actions, including an antioxidant effect, inhibition of Th2 cytokine, and improvement in barrier function, are involved.