Introduction: The aim of this study was to evaluate the gastric damage related to high dose radioactive iodine treatment during thyroid cancer treatment in an experimental rat model and evaluate histopathologically the radioprotective effect of amifostine. Methods and findings: 40 adult rats were enrolled into the study. Radioactive iodine treatment with 30 mCi/kg I131 was applied via orogastric tube simulating radioiodine ablation treatment (RAI) in thyroid cancer in all rats. After RAI subjects were divided into 2 groups: Group Orogastric RAI (Group OG, n: 20): Rats received no radioprotective agent but serum physiologic. Group Amifostine RAI (Group AP, n: 20): Rats received 200 mg/kg amifostine intraperitoneally 30 minutes before I131 application. On the 1st, 3rd, 5th and 7th days of experiment rats were sacrificed for histopathological evaluation. Gastric tissues were excised and tissue damage was assessed by using histopathological scoring. Total pathology score revealed a significant change on the 7th day. The subjects in Group OG had histopathological changes, while only one subject in Group AP was found to have pathologic changes (X2=39.7 df (28), p=0.04). The common histopathological findings were striking mucosal and intraepithelial leucocytic infiltration together with thinning of the mucosa, regenerative changes, and reactive atypia. Conclusions: RAI treatment causes gastric mucosal injury and amifostine was found to decrease radioactive iodine treatment related gastric damage.