Atopic dermatitis is a progressive inflammatory disease characterized by type 2 helper T cell (T2) reactivity. The aim of this study was to examine the therapeutic effects of Paeoniae radix alba root extract using a murine model of atopic dermatitis. Atopic dermatitis was induced in a murine model characterized by immune alterations skewed toward T2 reactivity and pathophysiological dermal alterations which resemble human atopic dermatitis. The root extract at 1% or 6% was applied to the mouse dorsal skin for 3 weeks following induction of atopic dermatitis. Splenocytes were stimulated with immobilized anti-CD3 for 48 h to measure cytokine production. Levels of serum IgE, IgG1, and IgG2a were quantitated. Epidermal thickness and numbers of skin mast cells were determined. Mice in which atopic dermatitis was induced displayed increased numbers of skin mast cells, increased frequency of scratching, elevated serum IgE levels, increased ratios of IgG1 to IgG2a, and ratios of IL-4 to IFN-γ. The frequency of scratching was significantly decreased following application of 1% or 6% extract for 1 week. The root extract also reversed T2 skewing, as serum IgE levels, ratio of serum IgG1 to IgG2a, and ratio of IL-4 to IFN-γ production by in vitro-stimulated splenocytes were all suppressed following application of 1% or 6% extract for 3 weeks. Taken together Paeoniae radix alba root extract is suggested to reverse the immunological alterations and skin manifestations symptoms found in atopic dermatitis.