Introduction Excessive iodine intake is emerging as a new healthcare-related concern. Excess iodine is associated with a spectrum of effects on the thyroid. Aim of work The aim of this study was to assess the effects of excess potassium iodide (KI) on the histological and immunohistochemical structure of the thyroid gland and evaluate the biochemical changes in thyroid hormones. Materials and methods Forty prepubertal male albino rats aged between 4 and 6 weeks were classified into two equal groups: group 1 (the control group), which was given distilled water, and group 2 (the KI-treated group), which was further subdivided into two equal subgroups. Subgroup 1a was given 0.1 mg KI/kg/day for 4 successive weeks and subgroup 1b was given 0.1 mg KI/kg/day for 8 successive weeks. At the end of the period, the animals were anesthetized and blood samples were collected for measurement of serum T3, T4, and thyroid-stimulating hormone. Thyroid glands were dissected out and processed for examination using light and electron microscopes. For light microscopic examination, the sections were s t a i n e d w i t h H & E a n d i m m u n o hi s t o c h e m i c a l a n a l y s i s w a s c a r r i e d o u t f o r localization of Fas. Results H&E-stained sections of the KI-treated subgroups showed highly significantly enlarged follicular cavities that were distended with vacuolated colloid. Most of the follicles were lined with flattened follicular cells with flattened nuclei. Follicular epithelial height was highly significantly decreased. Ultrastructurally, follicular cells showed dilatation of the cisternae of the endoplasmic reticulum, mitochondrial swelling, many electron-lucent zones, and collagen fibers in the interstitial spaces. Also, most of the nuclei were heterochromatic. Immunohistochemically, there was a highly significant increase in staining for Fas in the follicular cells of the treated subgroups. Biochemical assessment detected a nonsignificant decrease in T3 and T4 and a highly significant increase in the thyroid-stimulating hormone levels of the treated group. Conclusion Excessive iodine intake affects thyroid structure and function. Hence, public iodine intake should be regulated to make sure that it is within optimal levels. Proper monitoring of the salt iodization program is essential. Also, drugs with high iodine content should be administered with caution