Abstract: OBJECTIVE To explore the expressions of T cell immunoglobulin and mucin domain-3 (Tim-3) in patients with sepsis-induced acute lung injury (ALI) and observed its effect on regulating the alveolar macrophage polarization, inflammatory response, and metabolic reprogramming. METHODS A total of 22 patients with sepsis-induced ALI who were treated in First Affiliated Hospital of Shihezi University from Aug. 2022 to Dec. 2023 were enrolled in the study and were divided into the Tim-3 high-expression group with 11 cases (the H-Tim3 group) and the Tim-3 low-expression group with 11 cases (the L-Tim3 group) according to the expression level of Tim-3 mRNA in alveolar macrophages from bronchoalveolar lavage fluid (BALF). The mRNA expressions of alveolar macrophage M1 polarization markers inducible nitric oxidesynthase (iNOS), low affinity immunoglobulin gamma Fc region receptor III-A (CD16A), C-C chemokine receptor type 7 (CCR7) and human leukocyte antigen-DRβ1 (HLA-DRβ1) were detected by qRT-PCR. The levels of Tim-3 and inflammatory factors in BALF: tumor necrosis factor-α(TNF-α), transforming growth factor-β1 (TGF-β1), interleukin (IL)-6, IL-10 and IL-12,were detected by means of ELISA. The ratio of M1 to M2 macrophage was analyzed by flow cytometry. The metabolite profiles of BALF were observed by untargeted metabolomics. RESULTS The mRNA expression levels of MI polarization markers of the H-Tim3 group were lower than those of the L-Tim3 group (P＜0.05); as compared with the L-Tim3 group, the percentage of M1 (CD86⁺CD206^-) of the H-Tim3 group decreased by 11.51%, the percentage of M2(CD86^-CD206⁺) increased by 6.38%,and the ratio of M1 to M2 decreased by 50.00%( all P＜0.001). The levels of Tim-3 protein, TGF-β1 and IL-10 in BALF were higher in the H-Tim3 group than in the L-Tim3 group (P＜0.05). Metabonomics analysis showed that 9 types of lung-protective metabolites of the H-Tim3 group, including docosahexaenoic acid (DHA) and sphingosine, were upregulated remarkably, with the relative content of DHA differing most significantly, and it was as 40.54 times as much as that of the L-Tim3 group. CONCLUSIONS The high expression of Tim-3 may improve the lung function of the patients with sepsis-induced ALI by inhibiting M1 alveolar macrophage polarization, promoting the secretion of anti-inflammatory factors, and regulating the expression of protective metabolites. Tim-3 holds the value of being as a prognostic biomarker and a potential therapeutic target.