Background Thyroid gland affection by Fluorosis is documented in a number of previous studies. Resveratrol is a natural compound of plant origin. Its protective role was demonstrated previously in mice and rats against fluoride-induced hepatotoxicity and neurotoxicity. Aim to detect the thyro-protective role of Resveratrol in sodium fluoride rat model. Material and methods Forty adult male albino rats were distributed equally into: Group I (control): given 5 ml distilled water; Group II (Resveratrol): received 30 mg/kg Resveratrol; Group III (Sodium fluoride): given 10 mg/kg of Sodium Fluoride dissolved in 2.5 ml distilled water; Group IV (Sodium fluoride + Resveratrol): received 10 mg/kg of Sodium Fluoride and 30 mg/kg of Resveratrol. All doses were administered once daily by intra-gastric intubation. By the end of the experiment, rats were sedated by intra-peritoneal injection of Sodium thiopental; blood samples were collected, and thyroid lobes were dissected then processed for examination. Results In the control and Resveratrol groups, there were multiple variable follicles filled with homogenous eosinophilic colloid and lined with flat to cuboidal thyrocytes. Large pale-staining Para follicular cells. In the Sodium fluoride – treated group there were multiple dark stained nuclei of shrunken and exfoliated cells, areas of exudate and multiple layered follicular cells with high activity of Para follicular cells immuno-histochemically. Sodium fluoride+ Resveratrol – treated group appeared with almost preserved control appearance. Findings were confirmed using morphometric and electron microscopic studies. Conclusion Resveratrol supplementation with sodium fluoride restored almost all damaged appearance and functions of the thyroid cells to normal values. Further studies are necessary to examine the extended effect of Resveratrol with increased dosage or time of treatment.