Background: The present study was performed to determine the effect of amifostine in the prevention of radiation-induced acute and late period morphologic damages in rat kidney via light and electron microscopic examinations. Materials and Methods: Control rats (n=6) received saline solution 30 min before sham irradiation; the radiotherapy alone group (n=12) received saline solution 30 min before irradiation (a single dose of 15 Gy, applied unilaterally to the kidney) and a final radiotherapy +amifostine group (n=12) received 200 mg/kg amifostine 30 min prior to irradiation. Results: Microscopic examinations of irradiated kidneys revealed presence of glomerular tuft capsular adhesion, fusion of the foot processes and ballon-like cellular degeneration and loss of luminal brush border in tubules as early as eight weeks after irradiation. By 24 weeks post-irradiation, these changes were advanced and associated with focal mesangiolysis, segmental sclerosis and focal tubular atrophy. In addition, local irradiation caused interstitial fibrotic lesions in the kidney. Pretreatment of amifostine markedly prevented these glomerular and tubular changes, and interstitial fibrotic lesions. Conclusion: This study suggests that amifostine pretreatment may contribute to prevention of radiation-induced acute and late nephrotoxicity.