Abstract: Objective: To investigate the impact and possible regulatory mechanism of triggering receptor expressed on myeloid cells 2(TREM2) in lung ischemia-reperfusion injury(LIRI). Methods: Twelve male C57BL/6J wild-type mice(WT) and twelve TREM2 knockout mice(TREM2 KO) were randomly divided into four groups: WT micesham operation group(WT group), TREM2 KO mice sham operation group(TREM2 KO group), WT mice LIRI group(WT+LIRI group) and TREM2 KO mice LIRI group(TREM2 KO+LIRI group),with 6 mice in each group. The mouse LIRI model was prepared by occluding the hilum of the left lung for 1 h and reperfusion for 24 h in the WT+LIRI group and TREM2 KO+LIRI group, while only the hilum of the lungwas opened without occluding in the chest. Western blotting, immunofluorescence, reverse transcription-quantitative PCR(RT-qPCR), hematoxylin-eosin(HE) staining, and lung tissue wet-to-dry weight(W/D) ratio were performed to evaluate the impact of TREM2 knockout on tissue injury, inflammation and macrophage pyroptosis after lung ischemia-reperfusion in mice. Results: Knockout of TREM2 significantly exacerbated morphological changes in lung tissue after LIRI, increased lung injury scores(P<0.05), elevated the W/D ratio of lung tissue(P<0.05), promoted the expression of inflammatory factors interleukin-1β(IL-1β) and IL-18 in lung tissue after LIRI(P<0.05), and enhanced the expression of macrophage pyroptosis markers cysteine aspartic acid-specific protease-1(caspase-1) and pore-forming protein Gasdermin-D(GSDMD) in lung tissue after LIRI(P<0.05).Conclusion: TREM2 knockout can exacerbate LIRI, and its mechanism may be related to caspase-1-mediated pyroptosis of lung macrophages induced by the loss of TREM2.