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Objective: To investigate inhibition of dihydroartemisinin （DHA） on contact hypersensitivity （CHS） in mice and its mechanisms. Methods: Mice were sensitized with 0.5%2, 4-dinitrofluorobenzene （DNFB） on shaved abdominal flank skin for 2 consecutive days, and CHS was elicited by 0.25%DNFB on left ear 5 days later. Right ear was treated with acetone/olive-oil alone as control. Mice were given DHA orally 2 days before sensitization. Skin histopathological changes were observed by HE staining, infiltrations of CD4+T and CD8+T cells in ear skin were observed by immunohistochemical staining, and spleen index was detected. Serum IL-6, IFN-γ, IL-10, TGF-β and monocyte chemotactic protein （MCP）-1 changes were detected by ELISA, skin Smad2 and Smad3 phosphorylation levels were detected by Western blot, and skin and spleen immune cells infiltration were detected by flow cytometry. Results: DHA significantly improved ear swelling, skin erythema and spleen index of CHS mice （P<0.05）. Histopathological analysis revealed that degree of edema and cellular infiltration were markedly decreased in DHA-treated CHS mice. Flow cytometry results show that DHA treatment significantly decreased CD4+T cells, CD8+T cells, dendritic cells and macrophages infiltration in ear skin and spleen （P<0.05）. ELISA results showed that DHA treatment also diminished serum levels of IL-6, IFN-γ, TGF-β and MCP-1 compared with model group （P<0.05）. Western blot showed that Smad2 and Smad3 phosphorylation were normalized by DHA treatment （P<0.05）. Conclusion: DHA suppresses CHS by reducing infiltration of immune cells and regulating TGF-β/Smad signaling pathway, which provides a new drug selection and experimental basis for CHS treatment. [ABSTRACT FROM AUTHOR]