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Artemisiae Asiaticae Herba (AAH) has been used to remedy of symptoms such as bleeding, dysmenorrhea, eczema and itchy skin in Oriental Medicine. In this study, we investigated the protective effect of AAH on allergic response. The effect of AAH was analyzed by ELISA and RT-PCR in RBL-2H3 cells. We investigated cell viability, β-hexosaminidase and histamine as markers of degranulation, production of IL-4 and TNF-α, and gene expression of HDC2, cytokines and FcεRI αβγ subunit. We found that AAH suppressed β-hexosaminidase and histamine release, the production of IL-4 and TNF-α in RBL-2H3 by the anti-DNP IgE plus DNP-HSA stimulation. AAH also significantly decreased cytokine mRNA expressions, such as IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-12, IL-13, TNF-α, and GM-CSF, and increased cytokine mRNA expressions of IL-10 in RBL-2H3. In addition, AAH suppressed mRNA expression of FcεRI αβγ subunit on cell surface. Our results indicate that AAH protects against allergic response and exerts an anti-inflammatory effect through the inhibition of degranulation and production of cytokines and expression of FcεRI αβγ subunit.