Acute kidney injury (AKI) is a significant biomedical issue stimulated by many signaling pathways by lipopolysaccharide (LPS). This study looked at how fennel and khellah seed extracts (FSE&KSE) ameliorate the nephrosis that LPS-induced in experimental rats. Forty healthy adult male Westar albino rats weighing 200±20g, were used. Ten rats were left as control group G1, while other 30 rats were received a single intraperitoneal injection by LPS (12mg/kg b. wt.) and then divided into 3 groups 10 rats for each. G2 represented the positive control, however the remaining two groups treated orally by FSE and KSE for 4 weeks. The injection of LPS increased KIM-1 and NFAT-5 genes expression, inflammatory biomarkers, nephrotic proteinuria moreover histological and structural changes in kidney tissue, while administration of FSE and KSE resulted in a significant (P˂0.05) improvement in biochemical parameters and ameliorate structural changes in kidney tissue and down regulate of KIM-1and NFAT-5 genes expression related to protect kidney from LPS injury.