Cold plasma generated at atmospheric pressure has attracted intense interest in biomedical applications, particularly as an antimicrobial treatment. Here we report the therapeutic effect of humidified cold argon plasma on allergic contact dermatitis (ACD) in a mouse model. Treatment was carried out with different gas compositions: argon gas containing small amounts of either N2, O2, or H2O. The best effect was obtained using humid plasma (H2O addition), where the ACD symptoms decreased after one or two 1-min plasma treatments. Even for severe ACD with ulcers and crust formation, the humid plasma-treated mice recovered faster than the control group. Histopathological analysis by H&E-staining showed enhanced epithelialization with formation of collagen and hair follicles in the affected skin after humid plasma exposure. The therapeutic ability of the humid argon plasma discharge was proposed to be induced by reactive oxygen species (HxOy) transported from the discharge zone, which are adhesive and accumulate on the skin surface, penetrating the subcutis to eliminate inflammation. However, in treatments using plasma with addition of oxygen or nitrogen (without water) the active gaseous species are blocked due to poor adhesion to and penetration into the dry ACD skin, with correspondingly poor treatment effects. The enhanced in vivo healing in ACD mice indicate the non-thermal humid plasma could be a potential alternative approach for therapy of ACD and other inflammatory skin diseases.