© 2021 Elsevier Inc.Aims: In this study, we aimed to investigate the protective effect of apilarnil on kidney damage in the sepsis model induced by LPS. Main methods: 64 Sprague Dawley adult male rats were randomly divided into eight groups; control group, groups in which 0.2, 0.4 and 0.8 g/kg/bw apilarnil (API) was applied by oral gavage method for 10 days, LPS group in which 30 mg/kg/bw lipopolysaccharide (LPS) administered as intraperitoneally, groups in which LPS + 0.2, LPS+ 0.4 and LPS +0,8 API was applied. Six hour after the last administration the rats were anesthetized for euthanasia and kidney tissues were removed for RT-PCR analysis, immunohistochemical analysis and histopathologic analysis. Key finding: According to the results of RT-PCR expression levels of IL-6, IL-1β, NF-κB, TNF-α and TLR4 were significantly reduced in the LPS + 0,8 API group. Immunoreactivity of TLR4, pNF-κB and TNF-α levels in the LPS + 0.8 apilarnil group were significantly lower than in the LPS and LPS + 0.2 apilarnil groups. Histologically, compared to the LPS group the glomerular damage score tended to decrease in the LPS + 0,4 API and LPS+ 0,8 API groups, while the tubulointerstitial injury score decreased especially in the LPS + 0,8 API group. Significance: In the present study, 0,8 g/kg dose of apilarnil promoted potential renoprotective effects which were achieved, at least in part, by the modulation of important markers of the local immune response in the model of LPS-induced sepsis.