【Abstract】 Objective To investigate the expression and significance of MiR487b / IL33 / ST2 in sepsis. Methods Eighty patients with sepsis admitted to ICU from January 2015 to December 2017 in ICU and 80 volunteers in the same period were enrolled in this study. ELISA were used to detect interleukin33 and ST2. RTPCR were used to detect the expression of miR487b. The expression of miR487b and IL33 were exogenously regulated in mouse sepsis model. The levels of IL33, ST2, miR487b,TNFα and IL6 were detected. Luciferase reporter assay was implemented to verify the correlation between miR487b and IL33. Results Serum levels of IL33 and ST2 were significantly increased and miR487b was downregulated in patients with sepsis (P＜005). Serum IL33, ST2, TNFα and IL6 were upregulated in mice with sepsis (P＜005). Recovery of miR487b partially reversed the upregulation of IL33, TNFα and IL6. Luciferase reporter assay confirmed that miR487b directly negatively regulates IL33 expression (P＜005). Conclusion MiR487b can negatively regulate the IL33 / ST2 signaling pathway, induce the decrease of TNFα and IL6 expression and reduce the inflammatory reaction of sepsis, which is expected to become a new molecular target for the treatment of sepsis.