Background: Radioiodine I131 therapy (RAI) is an efficient method to decrease the functioning of very active thyroid tissues and to ablate the remnant thyroidal tissue after surgery and its metastases in differentiated thyroid carcinomas. Several cytoprotective, anti-oxidant or radioprotective mediators have been used in trials for RAI-induced damage in other organ systems. The hypothesis of this study was that zinc would ameliorate RAI-induced histopathological parameters in the rat gastrointestinal system. Materials and Methods: A total of 30 female Wistar albino rats were separated into 3 groups of 10. First group received only 0.003 mCi/g of I131, second group received 0.003 mCi/g of I131 and 0.01 mg/g of zinc and the control group (Sham Group) were given neither I131 nor zinc. Zinc was started via gastric gavage two days before I131 administration and continued for five days after RAI. At 24 hours after the last dosage of zinc, all the animals were sacrificed and the gastrointestinal tissues, including stomach, duodenum, ileum and colon were removed for histopathological examination. Results: All the histopathological parameters were diminished in the I131-zinc group compared to the I131 group. The histopathological differences were statistically significant in respect of inflammation and fibrosis between the I131-zinc group and the I131 group in all the evaluated gastrointestinal organs (p< 0.05). Conclusion: The co-administration of zinc was observed to significantly prevent RAI-induced histopathological alterations in rats.