Amiodarone is a very effective drug, widely used for tachyarrhythmias, but it is associated with many side effects involving different organ systems. The aim of this study was to elucidate the adverse effect of amiodarone on the thyroid gland and the possible protective role of vitamin E (α-tocopherol). The present study revealed that AMD administration resulted in loss of normal follicular architecture. Many follicles appeared shrunken. Many follicles were empty or contained scanty pale colloid. Some follicles appeared lined by more than one layer of cells. Others showed interruption of their basement membrane. Thickened collagen fibers in between the thyroid follicles were observed. Strong +ve PAS reaction in the basal lamina and cells lining the follicles and negative (–ve) to weak +ve reaction in the colloid filling the follicles were noticed. Sections of the thyroid gland of this group showed positive immune reaction to caspase-3 in the cytoplasm and nuclei of many follicular cells. The apical border of the follicular cells showed few irregular detached microvilli. The nuclei of the follicular cells were almost irregular and showed chromatin condensation. The cytoplasm of most follicular cells revealed numerous dilated rough endoplasmic reticulum. Numerous lysosomes were frequently seen. Some of these changes were irreversible during the recovery period. Supplementation of vitamin E (α tochopherol) with amiodarone improved these changes.