Nitrate is the most common contaminant in the world surface and ground water that is harmful to human health. Aim of work: The present work was performed to study the effect of chronic nitrate intake on the histological structure and function of the thyroid gland, to evaluate different dose response of nitrate in a constant period, moreover, to assess the possible role of vitamin E supplementation. Materials and Methods: 70 adult female albino rats were utilized and divided into three main groups. Group I (control) was subdivided into three equal subgroups: Ia received plain water only, Ib received 1ml/day corn oil (solvent of vitamin E) by oro-gastric tube and Ic received vitamin E 40 mg/kg body weight /day by oro-gastric tube. Group II (treated) was subdivided into three equal subgroups (IIa, IIb and IIc) and sodium nitrate was added to their drinking water in concentrations: 50, 150 and 500mg/l respectively. Group III (recovery) was coadministered sodium nitrate added to their drinking water at 500mg/l dose simultaneously with vitamin E 40mg/kg body weight /day by oro-gastric tube. After 12 weeks, all the animals were anaesthetized, the body weight was determined and blood samples were collected to measure serum thyroid hormones levels (total T3, T4 and TSH). The thyroid glands were dissected out and weighed then they were processed for light and electron microscope examination. Morphometric analysis was performed to measure the height of the follicular epithelium and the count of microfollicles. The obtained data were subjected to statistical analysis. Results: At high-dose nitrate exposure (150 and 500 mg/l), there were significant and dose dependent decrease in the body weight, increase in the thyroid gland weight, decrease in serum levels of total T3 and T4 and increase in serum level of TSH in comparison to the control group. By light and electron microscope examination, histomorphological changes and decreased immunohistochemical positivity for thyroglobulin were observed in the 150 and 500 mg/l nitrate groups. On the other hand, results of 50mg/l nitrate treated group and vitamin E given group appeared more or less similar to the control group. Conclusion: Prolonged nitrate ingestion exceeding 50 mg/l in drinking water affects the growth, induces morpho-functional modifications of the thyroid gland and may be considered as a goitrigenic factor. Furthermore, vitamin E ameliorates nitrate-induced toxicity. Therefore, routine analysis of public water and food; informing people about nitrate hazards and supplements of vitamin E are recommended.