Objective: To assess whether secretory otitis media may be caused by immune imbalance of Treg/Th17 mediated by PI3K/Akt/mTOR signaling, so as to find new therapeutic target. Methods: IL-17, TGF- and IL-6, IL-10 and Th17 cytokines were detected in peripheral blood of OME patients (PC group) and healthy people (NC group) by ELISA. The expression of ROR t mRNA and Foxp3mRNA in PBMC was detected by RT-PCR. OME rat model was established and the changes of lymphocytes in middle ear mucosa and spleen and PI3K/Akt/mTOR signaling in middle ear mucosa were detected by HE staining, IHC, WB and flow cytometry. Results: The immune imbalance of Treg/Th17 in secretory otitis media (OME) was confirmed by the expression of cytokines in OME serum and analysis of ROR T and Foxp3 mRNA which was Th17 and Treg specific transcription respectively. OME rat model further confirmed that Treg/Th17 imbalance could lead to OME as demonstrated by staining of MIDDLE ear mucosa and expression of ROR T and Foxp3. PI3K, Akt, and mTOR proteins were expressed in the MIDDLE ear mucosa of OME group and CON group, respectively. Compared with CON group, the expression of P-MTOR and P-PI3K proteins in the middle ear mucosa of OME group was significantly increased. Conclusions: Treg/Th17 imbalances are found in OME patients and OME animal model and the pathogenic mechanism may be due to systemic abnormal immune response, activated PI3K/Akt/mTOR signaling, abnormal T cell differentiation, leading to middle ear mucosal hyperemia, edema and subsequent occurrence of OME.