Rhubarb is a Chinese herb with a nephroprotective effect against HgCl2-induced acute kidney injury (AKI). Nuclear factor-ƙB (NF-ƙB) and neutrophil gelatinase- associated lipocalin (NAGL) are inflammatory biomarkers markedly increased in AKI. Downregulation of NF-ƙB and NAGL genes was found to blunt the pathophysiological consequences of renal damage. Developing a strategy to downregulate their expression might represent an efficient treatment for AKI. Aim: to elucidate whether rhubarb root extract can downregulate NF-ƙB and NAGL gene expression in HgCl2-induced AKI. Sixteen Wistar rats were equally divided into four groups: control group, extract group (12g rhubarb root extract /kg b.w., twice a week), positive control group (0.5 mg HgCl2/Kg b.w., twice a week.), treatment group (0.5mg HgCl2/Kg b.w. + 12 g rhubarb root extract /Kg b.w.) twice a week. By the end of the 8th week, all animals were sacrificed after ether anaesthesia, blood was collected for biochemical investigations (blood urea, serum creatinine, total protein, and albumin), and kidneys were removed for measurement of NF-ƙB and NAGL gene expression by RT-PCR, along with malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in kidney tissue. Results revealed significant (p<0.01) recovery in kidney weight and functions, MDA and TAC in the treatment group compared to positive control group. A highly significant (p<0.01) decrease was also observed in NF-ƙB and NAGL gene expression in the rhubarb root extract-treated group compared to the positive control group. Rhubarb root extract ameliorates HgCl2-induced AKI in rats through downregulation of NF-ƙB, and NAGL gene expression