Resveratrol is a natural product exhibit beneficial properties. Intestinal injury is a potential cause of death after high-dose radiation exposure. The study was assumed to determine whether resveratrol could modulate γ-rays-induced acute ileum injury in rats using biochemical and histopathological techniques. Rats were exposed to 8.5Gy-γ-rays and treated with or without resveratrol then, after 7-days post-irradiation, oxidative-stress; malondialdehyde (MDA), total nitrate/nitrite (NO(x)), and myeloperoxidase), antioxidant; superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd), anti-inflammatory markers; tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, and histopathological study were evaluated in intestinal wall. Data has revealed a significant reduction in radiation-induced lipid-peroxidation (MDA), total NO(x), myeloperoxidase), inflammatory markers (TNF-α and IL-6) and escalation in antioxidant enzymes (SOD, GPx and GRd). In resveratrol and γ-rays treated rat group, obvious modulation in γ-rays-induced histopathological injury into villi and crypts of the ileum mucosa were distinguished. Resveratrol exhibits radio-protective effects against whole-body radiation-induced acute ileum injury in rats, for the first time and thus, could be of clinical value for patients undergoing radiotherapy.