【Abstract】 Objective To investigate the role of miR-140 targeting PD-L1 in immunosuppression of sepsis in mice. Methods Ninety mice were randomly divided into control group (control group), sepsis model group (CLP Group) and CLP+Mir-140 group with 30 mice in each group. Sepsis model was established by cecal ligation and puncture (CLP). Mir-140 was transfected into the tail vein The expression of TNF-α and IL-2 in serum was detected by ELISA. The percentage of CD4+ T and CD8+ T cells in serum was detected by flow cytometry. Peritoneal macrophages were extracted. The positive rate of PD-L1 was analyzed by flow cytometry. The expression of Mir-140 and PD-L1 gene was detected by RT qPCR The expression of PD-L1 protein was detected by tern blot, and the relationship between Mir-140 and PD-L1 was detected by luciferase reporter assay. Results Compared with the control group, the levels of TNF-α and IL-2 in CLP Group increased on day 1, day 7 and day 14 (P＜0.01), but decreased in a time-dependent manner (P＜0.05). Compared with the control group, the survival rate of CLP Group was lower than that of control group (P＜0.01), the percentage of CD4+ and CD8+ cells increased (P＜0.01), the PD-L1 positive cell rate of macrophages was increased (P＜0.01), the expression of Mir-140 was decreased (P＜0.01), and the expression of PDL1 gene and protein was increased in CLP Group (P＜0.01). Compared with CLP Group, the survival rate of mice in CLP+Mir-140 group increased (P＜0.01), the percentage of CD4+ and CD8+ cells increased (P＜0.01), PD-L1 positive cell rate decreased (P＜0.01), Mir-140 expression level increased (P＜0.01), and Pd L1 gene and protein expression levels decreased in CLP+Mir-140 group (P＜0.01). The results of luciferase assay showed that Mir-140 and PD-L1 had a targeted relationship. Conclusion Mir-140 can target PD-L1 and improve the immunosuppression induced by sepsis in mice.