Objective <p>The objective of this study was to explore the mechanisms by which urine - derived stem cell exosomes (USCexo) alleviate sepsis - related acute kidney injury (SAKI), as acute kidney injury often complicates sepsis with unclear role of USCexo in SAKI while stem cell exosomes show potential in AKI treatment.</p> Methods <p>Human urine - derived stem cells (USCs) were isolated from human urine and characterized via flow cytometry. A sepsis - related acute kidney injury mouse model was induced by cecal ligation and puncture (CLP). The mice were divided into a control group receiving phosphate - buffered saline (PBS) and an experimental group receiving USCexo via tail vein injection. Survival rate, renal damage evaluated by HE staining, and renal function assessed by sCr and BUN levels were measured. Renal RNA was extracted to analyze apoptosis and oxidative stress. In vitro, qRT - PCR was used to assess the inflammatory response in macrophages treated with USCexo.</p> Results <p>Treatment with USC - derived exosomes led to a reduction in the levels of pathological injury, sCr, and BUN. It inhibited renal cell apoptosis and oxidative stress, decreased the infiltration of inflammatory cells, and protected renal function in SAKI mice. Additionally, USCexo suppressed the inflammatory response of primary peritoneal macrophages induced by lipopolysaccharide (LPS).</p> Conclusions <p>USC - derived exosomes protect against SAKI by inhibiting oxidative stress and inflammation, which provides a theoretical basis for the potential use of USCexo in the treatment of SAKI.</p> Clinical trial number <p>Not applicable.</p>