Context: Dehydroxymethylepoxyquinomicin (DHMEQ) which is originally developed as an analog of antibiotic epoxyquinomicin C is a specific and potent inhibitor of NF-kappa B and has been shown to possess promising potential as an anti-inflammatory and anti-tumor agent. Objective: This study examines DHMEQ's effect on therapeutic potential for atopic dermatitis (AD)-like lesions. Materials and methods: AD lesions were chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in BALB/c mice. The mice were then externally treated with DHMEQ ointment. Macroscopic and microscopic changes of the skin lesions were observed and recorded. Results: DHMEQ inhibited ear swelling and relieved clinical symptoms of the AD-like lesions induced by DNCB/OX in BALB/c mice. Histopathology examination illustrated that it significantly decreased DNCB/OX-induced epidermal thickness, the infiltration of inflammatory cells, and the count of mast cell. The elevated level of immunoglobulin E (IgE) in serum and the mRNA levels of interferon gamma (IFN-gamma), interleukin 4 (IL-4) and IL-13 in the ear tissues, were also suppressed by DHMEQ. Discussion and conclusion: This study indicated that DHMEQ would be useful for the treatment of AD.