Abstract: Objective To investigate the therapeutic efficacy of Qingxin Yunpi Formula (QXYPF) in a mouse model of food allergy (FA)-associated atopic dermatitis (AD) induced by 2,4-dinitrochlorobenzene (DNCB) and ovalbumin (OVA). Methods Male BALB/ c mice were randomly divided into six groups (n= 10 per group):control, AD, model, QXYPF low-dose ( QXYPF-L), QXYPF high-dose ( QXYPF-H), and prednisone ( PNS).Except for the control and AD groups, FA-AD was induced by epicutaneous application of DNCB on the dorsum combined with intraperitoneal OVA injection; the AD group received DNCB application only. Post-modeling assessments included: clinical evaluation of dorsal lesions, dermatitis severity scoring, quantification of scratching behavior, histopathological examination of skin sections to determine epidermal thickness and mast cell infiltration,enzyme-linked immunosorbent assay (ELISA) measurement of serum OVA-specific IgE (OVA-sIgE) levels, and of T-helper (Th) 2 cytokines (IL-4, IL-5) and Th1 cytokine (IFN-γ), and immunohistochemical analysis of IL-4, IL-5, and IFN-γ in lesioned skin tissues. Results Compared with the control group, mice in the model groups exhibited more severe dorsal skin lesions, increased dermatitis scores and scratching frequencies (P<0. 05). The model group showed significantly thickened dorsal epidermis (P<0. 05), acanthosis, and noticeable inflammatory cell infiltration in the dermis. Serum levels of OVA-sIgE, IL-4, and IL-5 were elevated ( P<0. 05), while IFN-γ levels were decreased in both AD and model groups ( P<0. 05). Additionally, protein expression of IL-4 and IL-5 in dorsal lesional tissues was increased in the model group (P<0. 05), whereas IFN-γ protein levels were reduced in both AD and model groups (P<0. 05). In comparison with the model group, all treatment groups demonstrated improved dorsal skin lesions, significantly reduced dermatitis scores and scratching frequencies ( P<0. 05), markedly alleviated epidermal thickening (P<0. 05), improved acanthosis, and reduced inflammatory infiltration in the dermis. Serum OVA-sIgE levels were decreased (P<0. 05), along with reduced serum IL-4 and IL-5 levels and increased IFN-γ levels (P<0. 05). Protein expression of IL-4 and IL-5 in lesional skin tissues was downregulated, while IFN-γ protein expression was upregulated (P<0. 05). Conclusions QXYF ameliorates skin lesions and pruritus in FA-AD mice,potentially by inhibiting Th2-related cytokines and promoting Th1-related cytokine expression.