Acute renal injury is a common and hazardous distress of γ-rays' exposure. Aim: The aim of the current study was to explore the role of Eugenol on γ-rays-induced acute kidney lesions in rats. The rats were separated into four groups (n=6). The control group received saline for two weeks. The Eugenol group received i.p. 20 mg/kg Eugenol for two weeks. The γ-rays group was pretreated with saline for a week, then whole-body exposed to 8 Gy γ-rays and saline treatment continued for another week. The rats in γ-rays+ Eugenol group received Eugenol for a week pre-irradiation, then were exposed to γ-rays and Eugenol treatment continued for another week. The blood and kidney samples were collected for histopathological and biochemical investigations. Exposure to γ-rays induced atrophy of glomeruli with increasing capsular space, expanded renal tubules and congested inter tubular blood vessels. Histological changes were accompanied by significant decreases in the level of antioxidants: reduced glutathione content (GSH), and superoxide dismutase (SOD), and catalase (CAT) activities with a significant increase of malondialdehyde (MDA; end-product of lipid peroxidation), indicating oxidative stress. Significant increases in the levels of inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-1 Beta (IL-1β) levels were recorded also. Kidney damage was substantiated by significant increases in urea, creatinine, lactate dehydrogenase (LDH), γ-glutamyltransferase (γGT), and disturbance of electrolytes balance; elevated sodium (Na⁺), and decreased potassium (K⁺). Eugenol treatment has significantly improved histological damage, oxidative stress and inflammation accompanied by amelioration of kidney functions. Eugenol treatment has significantly improved histological damage oxidative stress and inflammatory-biomarkers, which was accompanied by significant amelioration of kidney functions. Conclusion: Eugenol may alleviate acute kidney injury resulting from g-rays exposure through antioxidant and anti-inflammatory properties.