Allergic conjunctivitis (AC) is a common allergic condition worldwide that requires accurate screening and early diagnosis. We found that gp130 is essential for AC, as gp130 levels are elevated in AC. Therefore, this study aimed to elucidate the functions and the possible underlying mechanisms of gp130 in AC.To compare mRNA expression profiles, the conjunctival tissues of BALB/c mice with ovalbumin (OVA)-induced AC were subjected to RNA-sequencing (RNA-seq) analysis followed by bioinformatic analysis. A nonrandomized study involving 57 patients with AC and 24 sex- and age-matched healthy individuals was conducted. A protein chip was used to detect cytokine levels in patient tears. Differentially expressed proteins in patient serum were detected using label-free quantitative mass spectrometry. Histamine-stimulated conjunctival epithelial cells (HConEpiCs) were used to construct a cell model. LMT-28 which can inhibit gp130 phosphorylation was dropped onto the murine ocular surface, and the resulting symptoms were observed.Gp130 is upregulated in the conjunctival tissues of OVA-induced mice, the serum and tears of patients, and the histamine-stimulated HConEpiCs. Signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2) were upregulated in the conjunctival tissues of mice with OVA-induced AC and in HConEpiCs. Ocular surface inflammation was significantly relieved in LMT-28-treated mice. The expression of IgE, IL-4, IL-5, and IL-13 in serum of LMT-28-treated mice decreased. The number of mast cells in conjunctival tissue was decreased compared with OVA-induced mice.Gp130 may play an important role in AC via the gp130/JAK2/STAT3 pathway. Inhibiting gp130 phosphorylation alleviates ocular surface inflammation in mice, presenting a potential treatment approach for AC.