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Moringa oleifera popularly referred to as wonder plant is a medicinal plant with a remarkable variety of therapeutic purposes. The aim of this study was to assess the ameliorative effect of Moringa oleifera on glycerol-induced acute kidney injury in rats thus renewing interest in the development of new treatment plans. Glycerol (50% v/v in sterile saline, intramuscular) was used to induce acute kidney injury. Group A (control group) received distilled water only, the group B animals (toxicant group) received glycerol alone on the 8th day, and groups C and D animals were given 50 mg/kg and 100 mg/kg of methanol stem extract of Moringa oleifera respectively for seven days and glycerol on the 8th day. Group E animals on the other hand received 100 mg/kg of methanol stem extract of Moringa oleifera alone for seven days and on day 8 received normal saline. To assess renal damage and possible ameliorative effects of the extract, serum blood urea nitrogen (BUN), creatinine, myeloperoxidase, advanced oxidative products, malondialdehyde, superoxide dismutase, reduced glutathione, and protein carbonyl were determined. Histopathological analysis of kidney tissues and immunohistochemical analysis of KIM-1 and NF-ҝB expressions were also carried out on kidney tissues. The results showed that methanol stem bark extract of Moringa oleifera improves glycerol-induced acute kidney injury by inhibiting markers of inflammation, oxidative stress and renal damage by modulating KIM-1 and NF-ҝB signaling pathways. In conclusion, the methanol stem extract of Moringa oleifera blunts glycerol-induced acute kidney injury in rats through its anti-oxidant and anti-inflammatory properties.