Tributyltin is used in industrial applications. This current research aimed to study the effect of Tributyltin on the thyroid gland structure and function of adult male albino rats and the protective effect of Lycopene. Twenty-one male adult albino rats were classified into three groups: Control, treated that received Tributyltin, and protective that received Lycopene with Tributyltin. At the end of the experiment, blood samples were collected and T4, T3, and (TSH) were measured. Tissue superoxide dismutase (SOD) and malondialdehyde (MDA) were estimated. Thyroid gland specimens were processed for histological and immunohistochemical examination. Then morphometric and statistical analyses were done. The treated group showed affection in thyroid function and histological structure as vacuolated colloid and cytoplasm and dark nuclei. Ultrastructurally, follicular cells showed irregular shrunken nuclei, atrophied apical microvilli, vacuoles, multiple lysosomal granules, mitochondria with destructed cristae, and extensively dilated rough endoplasmic reticulum. There was increase in Caspase-3 immunoexpression and decrease in Beclin-1 immunoexpression. The thyroid structure and biochemical markers improved after Lycopene administration. The thyroid gland damage caused by Tributyltin is ameliorated by Lycopene.