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Objective To investigate the effect and mechanism of let-7e-5p on allergic rhinitis in mice. Methods Eighteen BALB/c mice were randomly divided into the control group, the allergic rhinitis (AR) group, the let-7e-5p agonist negative control (AR+agomir-NC) group, the let-7e-5p agonist (AR+agomir) group, the let-7e-5p inhibitor negative control (AR+antagomir-NC) group and the let-7e-5p inhibitor (AR+antagomir) group. Except the control group, the other groups were sensitized with ovalbumin (OVA) to establish AR model. The AR+agomir group and the AR+antagomir group were treated with let-7e-5p agomir or let-7e-5p antagomir at the same time for intervention. After the last sensitization, the allergic rhinitis of mice were scored. HE staining was used to observe nasal mucosa. The number of eosinophils was counted. Real-time PCR was used to detect mRNA expression levels of let-7e-5p, Fas and FasL, and Western blot assay was used to detect protein expression levels of Fas and FasL. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of immunoglobulin E (IgE), specific immunoglobulin E (sIgE), interferon gamma (IFN-γ), interleukin (IL)-12, IL-4 and IL-13. The targeting relationship between let-7e-5p and Fas and FasL were analyzed by dual luciferase assay. Results Compared with the control group, the allergic rhinitis score was increased in the AR group, nasal mucosa hyperplasia was obvious and the number of eosinophils was increased. The expression levels of let-7e-5p and IFN-γ and IL-12 were decreased, while the expression of Fas and FasL and levels of IgE, sIgE, IL-4 and IL-13 were increased (all P＜0.05). Compared with the AR+agomir-NC group, the allergic rhinitis score was decreased in the AR+agomir group, the nasal mucosa structure was clear and the number of eosinophils was reduced. The expression of let-7e-5p and levels of IFN-γ and IL-12 were increased, while the expression of Fas and FasL and levels of IgE, sIgE, IL-4 and IL-13 were decreased (all P＜ 0.05). Compared with the AR+antagomir-NC group, the allergic rhinitis score was increased in the AR+antagomir group, the nasal mucosa was significantly thickened, and the number of eosinophils was increased. The expression of let-7e-5p was decreased, and the expression of Fas, FasL and levels of IgE, sIgE, IL-4 and IL-13 were increased (all P＜0.05). There were no significant differences in IL-12 and IFN- γ between the AR+antagomir-NC group and the AR+antagomir group (P＞ 0.05). Compared with the NC+3'UTR-WT group, luciferase activity was decreased in the let-7e-5p agomir+3'UTR-WT group (P＜0.05). Conclusion Let-7e-5p may affect the balance of T helper type 1 (Th1)/ T helper type 2 (Th2) cells by targeting Fas/FasL, and thus participate in the progression of AR in mice. [ABSTRACT FROM AUTHOR]