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The objective of this study was to investigate the effect of high salt conditions on basophil (KU812) degranulation and the expression of related cytokines and to preliminarily explore its molecular mechanism. Enzyme linked immunosorbent assay (ELISA) and real-time fluorescence quantitative polymerase chain reaction (qPCR) were used to measure the changes of bioactive mediators and pro-inflammatory cytokines released by KU812 cells after degranulation under high salt conditions. The effects of serum- and glucocorticoid-regulated kinase 1 (SGK1) inhibitor and p38 inhibitor on the production of interleukin (IL)-4 by KU812 cells were detected by qPCR. The results showed that high-salt conditions could not promote the degranulation of KU812 cells to rel ease bioactive mediators such as histamine and β-hexaminosidase (β-HEX), but instead enhance the production of pro-inflammatory factors such as IL-6 and tumor necrosis factor (TNF)-α. High-salt conditions could also promote the production of IL-4 by KU812 cells and led to high expression of the SGK1 gene. It was also found that both SGK1 inhibitor and p38 inhibitor could significantly inhibit the expression of SGK1 and IL-4 in KU812 cells under high salt conditions. These results indicated that high-salt conditions could promote the production of IL-4 by KU812 cells through the p38-SGK1 signaling pathway.