Objective To investigate the anti-atopic dermatitis (AD) effects of oxymatrine in a murine model of AD. Methods (1) Kunming mice were randomly divided into five groups: Blank Control group(BC), model control group (DEX), positive control group(DXM), OXY-L and OXY-H groups (50 and 100 mg / kg) oxymatrine groups. Vehicle or oxymatrine was orally administered twice daily for 7 times. Ten minutes after the last administration, 50 μL of dextran was injected subcutaneously into the left hind foot pad of each mouse. The number of times the mouse licked the hind foot within 15 min was observed and recorded. (2) BALB/ c mice were randomly divided into 6 groups: blank control group(BC), model control group(DNCB), positive control group (DXM), OXY-L, OXY-M and OXY-H groups ( 25, 50 and 100 mg / kg) oxymatrine groups. Except for the blank control group, the other groups were treated with 2,4-dinitrochlorobenzene (DNCB) solution repeatedly to establish the AD model. From the first day of the experiment, vehicle or drugs were orally administered once daily for 14 d. Changes in weight were observed and recorded, and the organ coefficients of the spleen and thymus were determined. The contents of total IgE and T helper 2 (Th2) cytokines in the peripheral blood were detected using enzyme- linked immunosorbent assay kits. In addition, hematoxylin and eosin staining was used to observe the pathological changes of skin lesions, and toluidine blue staining was used to evaluate the infiltration of mast cells in skin lesions. Results Oral administration of oxymatrine significantly decreased the number of scratches in the itching model mice (P<0. 01). After 14 d of treatment with oxymatrine by gavage, the eczema-like dermatitis of the AD model mice was relieved, and thickening of the dermis, infiltration of inflammatory and mast cells, and intercellular edema were reduced. The expression of total IgE and Th2-type cytokines, such as interleukin IL-4 and IL-13, was significantly lowered in the peripheral blood ( P< 0. 05). Conclusions Traditional Chinese medicine refers to the experience and knowledge summarized by Chinese people in the long-term practice of diagnosis and treatment of diseases. Oxymatrine, an effective component of the commonly used Chinese medicine Sophora flavescens, has a therapeutic effect on AD mice. Its mechanism is related to a reduction in the infiltration of mast cells in the skin dermis and the reduced expression of Th2-type cytokines.