<p><?tk 2?>Sepsis is a systemic inflammatory response that often leads to multiple-organ dysfunction, particularly intestinal injury, which worsens prognosis. This study aims to explore the effects of exosomes derived from mesenchymal stem cells (MSCs) on intestinal injury in sepsis and their underlying mechanisms. Bioinformatics analyses of sequencing data from mouse models of spesis and lipopolysaccharide-treated intestinal epithelial cells were conducted to identify candidate genes and pathways involved in intestinal damage. Human umbilical cord MSCs were isolated, and their exosomes were administered to mouse models of spesis. Various assays were conducted to evaluate the protective role of MSC-derived exosomes. The bioinformatics analyses revealed upregulation of miR-218-5p and downregulation of Chromobox homolog 8 (Cbx8) in mouse models of spesis. Experimental results showed that exosome treatment significantly reduced intestinal inflammation, necrosis, cytokine levels (e.g., IL-1β, IL-6), and apoptosis-related proteins (e.g., caspase-3, Bax). Exosomes also restored the miR-218-5p-Cbx8 axis, confirming the bioinformatics findings. Overall, this study highlights that MSCs-derived exosomes offer a promising therapeutic strategy for sepsis-induced intestinal injury by reducing inflammation and apoptosis while modulating the miR-218-5p-Cbx8 axis, demonstrating their potential application in sepsis and other inflammatory diseases.</p> Graphical Abstract <p></p>