Objective In order to explore the therapeutic efficacy of Dendrobium officinale polysaccharides on atopic dermatitis(AD)mice and its effects on gut microbes.Methods The mice were randomly divided into control group(three mice),AD group(four mice)and AD+Dendrobiumfugitivei polysaccharide group(four mice).Comparison of clinical manifestations(scratching times,skin lesion score,ear swelling)of the three groups of mice,HE staining was used to observe the pathological damage of skin tissue.The levels of IgE,interleukin-4(IL-4)and interferon-γ(IFN-γ)in the peripheral blood and skin lesions of the three groups of mice were examined by enzyme-linked immunosorbent assay(ELISA).The levels of IL-4 and IFN-γ mRNA in the three groups of mice were detected by quantitative polymerase chain reaction(qPCR).The mouse feces of three groups were collected for 16S rRNA gene sequencing.Results Compared with the control group,AD mice developed pathological manifestations such as erythema,edema,epidermal exfoliation and scaling,the skin lesion score was significantly increased;hyperkeratosis accompanied with hypokeratosis,hypertrophy of the spine,obvious inflammatory cell infiltration and telangiectasia were observed in the epidermis and dermis;the expression levels of inflammatory factors in serum and skin lesions were significantly increased;the abundance of Bacteroides and Staphylococcus increased in the intestinal flora,while the abundance of Muri,Prevotella,Lachnospiraceae-NK4A136-group decreased.After the intervention of Dendrobium officinale polysaccharides,the pathological condition,skin lesion score,skin lesion severity,inflammatory factor expression and differential flora abundance of AD mice were improved.Conclusion Dendrobium officinale polysaccharides can exert pharmacological effects by regulating the balance of gut microbiota and reducing inflammatory response,and can effectively relieve the skin lesions of AD.