Introduction: The thyroid gland plays an important role in human health. Fluoride disturbs the synthesis and secretion of thyroid hormones. Selenium at nano size (Nano- Se) has an equal efficacy like selenium as an antioxidant but with reduced risk of its toxicity. Aim of the work: This study was done to evaluate the effect of sodium fluoride on the structure and function of the thyroid gland and to throw more light on the role of selenium nanoparticles (Se-NPs) as a new line of therapy. Information about recovery of thyroid gland after stoppage of sodium fluoride was also investigated. Material and Methods: Forty eight adult male albino rats were divided into four equal groups; control group, fluoride-treated group, fluoride and SeNPs treated group and fluoride recovery group. At the end of the experimental period, blood samples were collected for serological study (T3, T4 and TSH) and thyroid specimens were processed for light and electron microscope examination. Results: Histological examination of thyroid gland showed marked structural changes with decreased level of thyroid hormones in fluoride treated group. These changes were slightly decreased in fluoride recovery group while improved in fluoride and SeNPs treated group. Conclusion: Se nanoparticles can improve the adverse effects of sodium fluoride on the thyroid gland. The antioxidant activity of Nano-Se may be a major reason for its positive impact on the thyroid fluorosis. On the other hand, fluoride induced thyroid damage could be partially reversed by stoppage of sodium fluoride treatment. Recommendation: Selenium nanoparticles could be considered to be experimentally effective in case of thyroid fluorosis. The therapeutic benefits of Se-NPs will make them the first drug of choice in the future.