Background: Amiodarone (AMD) is a benzofuran derivative, used in the management of angina and refractory ventricular arrhythmia. AMD may lead to either hypothyroidism or hyperthyroidism, depending on the daily dietary allowance of iodine. Aim of the Work: The aim of the current study is to investigate the structural and biochemical changes of the thyroid gland of adult male albino rats after exposure to different doses of AMD. Material and Methods: Thirty adult male albino rats were used in the experiment, they were divided into three groups; the Control group (Group I, N=10); AMD therapeutic dose-treated group (Group II, N=10), received AMD at a dose of 30 mg/Kg daily for 12 weeks by oral gavage; AMD toxic dose-treated group (Group III, N=10), received AMD at a dose of 60 mg/Kg daily for six weeks by oral gavage. At the end of the experiment, blood samples were taken from rats to estimate the serum concentration of tri-iodothyronine (T3), thyroxine (T4), and thyrotrophin (TSH). The thyroid glands of all rats were removed, and specimens from the glands were prepared and processed for histological examination under a light microscope. An immunohistochemical study was conducted using Caspase III. Results: Biochemical examination revealed a highly significant increase of serum T3 and T4, with Concomitant suppression of TSH. Histopathological examination of thyroid tissues from AMD therapeutic dose group (Group II) showed marked evidence of thyrotoxicosis in the form of microcystic follicular changes and peripheral scalloping, cellular degeneration with scanty cytoplasm and vesicular nuclei appeared. These changes became more severe in AMD toxic dose group (Group III) in the form of epithelial hyperplasia with atypical nuclear features, together with thyroid tissue damage with hemorrhage and necrosis. Conclusion: Amiodarone had detrimental effects on the rat's thyroid tissue when administered either in therapeutic or toxic doses.