Qingpeng ointment (QP) is a Chinese medicine which has been used in treatment of atopic dermatitis (AD) in China. AD-like lesions were induced in BALB/c mice by repeated application of 2,4-dinitrofluorobenzene (DNFB) on shaved backs. The mice were then treated for 2 weeks with QP of different concentrations and Mometasone Furoate cream (MF), respectively. Macroscopic and microscopic changes of the skin lesions were observed after the treatment. The levels of serum immunoglobulin (Ig) E, tissue interferon (IFN)-γ, and interleukin (IL)-4 and IL-17A and the levels of involucrin, filaggrin, and kallikrein7 in epidermis were measured. The results show severe dermatitis with immune profiles similar to human acute AD. A significant infiltration of CD4+ T and mast cells was observed in dermis of lesion but inhibited by QP after a 2-week treatment with it. The production of IgE, IL-4 and the mRNA expression of IL-17A were also suppressed, but the level of IFN-γ was increased. MF suppressed all production of these cytokines and IgE. Accordingly, the mechanism of QP on AD might correlate with its ability of modulating the immune dysfunctions rather than suppressing them. It had no effect on expressions of involucrin and filaggrin, except that its vehicle decreased the level of kallikrein7.