The purpose of this study was therefore to investigate the effects of radiotherapy on the kidney and the potential use of agents such as N-acetylcysteine (NAC) in developing a future therapeutic protocol for radiation-induced nephrotoxicity at the histopathological and biochemical levels. Our study consisted of three groups: control (oral saline solution only; group 1), irradiation (IR; group 2), and NAC + IR (group 3). The irradiation groups received a single dose of whole-body 6-Gy x-irradiation. The NAC group received 300 mg/kg by the oral route for 7 days, from 5 days before irradiation to 2 days after. All subjects were sacrificed under anesthesia 2 days after irradiation. IR increased tubular necrosis scores (TNS), MDA, and caspase-3 expression, while reducing renal tissue GSH levels. We also observed dilation in renal corpuscles and tubules. Capillary congestion was present in the intertubular spaces. NAC reduced the levels of TNS, MDA, and caspase-3 expression, but increased the levels of renal tissue GSH. ROS-scavenging antioxidants may represent a promising means of preventing renal injury in patients undergoing radiotherapy.