Sepsis is a life threatening systemic inflammatory response syndrome, often leading to multiple organ dysfunction syndrome (MODS). However, whether interorgan crosstalk exist between kidney and lung during sepsis, and the mechanisms and mediators are not well understood. In this study, we provide the first conclusive evidence that the kidney-derived extracellular vesicles (EVs) are involved in remote lung injury during sepsis. Using proteomics analysis, we demonstrated that sepsis triggered the formation of mitochondrial-derived vesicles (MDVs) by upregulating sorting nexin 9 (SNX9) in renal tubular epithelial cells (TECs), released extracellular as mitochondria-rich EVs (mitoEVs), and then entered circulation. Next, using in vivo EVs administration and target inhibition of EVs releasing from renal TECs in a septic model, we define an axis through which renal TECs-derived mitoEVs mediated remote lung injury during sepsis. Further single-cell RNA sequencing analysis revealed that renal TECs-derived mitoEVs targeted lung endothelial cells, shifted endothelial cells to a proinflammatory phenotype, impaired endothelial integrity and promoted immune cell accumulation. Mechanistically, renal TECs-derived mitoEVs activated the cGAS-STING pathway in lung endothelial cells by transferring mitochondrial DNA (mtDNA), and ZBP1 served as a cooperative partner for cGAS-STING pathway activation. Additionally, early detection of plasma mitoEVs provides a valuable biomarker for identifying acute respiratory distress syndrome (ARDS) and predicting the mortality as well. These findings advance our understanding of EVs-facilitated interorgan communication during sepsis-related MODS and further suggest potential therapeutic strategies targeting SNX9/MDVs (kidney)-mitoEVs (circulation)-mtDNA/cGAS/STING (lung) axis to alleviate sepsis-related ARDS.