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Background: A potentially fatal complication of sepsis is septic acute kidney injury. Stem cell therapy is a potential new method of treating sepsis and has been applied to treat some human diseases., Objectives: This study investigated the effects of secretome-MSCs on NGAL, CRP, NF-κB, and MMP-9 proteins, and histopathology in mice with septic AKI., Methods: A post-test-only group design was conducted in 30 Balb/C male mice, which were randomly assigned to five groups: the control group was intraperitoneally injected with 0.5 ml of 0.9 % NaCl, the septic AKI, and the treatment groups (T1, T2, and T3) were intraperitoneally injected with 0.5 ml of 0.9 % NaCl and 0.3 mg/kg BW LPS single dose for three days. Three-day treatments of 150, 300, and 600 µl secretome-MSCs were administered intraperitoneally into the treatment groups. Furthermore, kidney and blood samples were collected for biochemical and histopathological analyses., Results: The T1, T2, and T3 groups had lower expression of NF-κB and MMP-9 and significantly lower CRP and NGAL levels than that of septic AKI group. T1 (1.21 ± 0.19), T2 (0.75 ± 0.22), and T3 (0.38 ± 0.14) groups demonstrated lower average scores for inflammation, necrosis, hemorrhage, and degeneration compared to septic AKI group (2.17 ± 0.13)., Conclusions: Administration of 600 µl/20 g BW secretome-MSCs suppresses NF-κB and MMP-9 expression and reduces CRP and NGAL levels. Meanwhile, the 150 and 300 µl/20 g BW doses also indicated a greater improvement in renal tissue damage of mice with septic AKI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)