The aim of this study was to evaluate if a composition of herb extracts, PLX-PLS was effective to treat atopic dermatitis (AD) in mice. SPZZC is a composition of herb extracts containing the roots of Scopolia parviflora and Paeonia lactiflora, the herb of Zizania caudiflora, the fruit of Ziziphus jujuba and the leaf of Chinese arborvitae. AD in BALB/c mouse was induced by patching ovoalbumin on the backside, while it in NC/Nga mouse was induced by repeated application of 1-chloro 2,4-dinitrobenzene (DNCB). Mice were topically treated with SPZZC or Domohorn ointment on the backside for 2 weeks (BALB/c) or 1 week (NC/Nga). Scratching behavior, clinical skin severity and the levels of WBC, neutrophil, eosinophil and total serum IgE were measured. After AD induction, scores of scratching behavior and clinical skin severity and the levels of WBC, neutrophil, eosinophil and total serum IgE were increased. Treatment with SPZZC significantly decreased scores of scratching behavior and clinical skin severity in a dose dependent manner in NC/Nga and BALB/c mice. Treatment with SPZZC 2% significantly decreased also the levels of WBC, neutrophil, eosinophil and total serum IgE. Especially, treatment of SPZZC 2% reduced more rapidly score of clinical skin severity than clobetasol cream. These results suggest that the SPZZC may be an alternative substance for the management of AD.