Background: Thyroid hormone is critical for the normal physiological function of almost all mammalian tissues. Perfluorooctanoic acid (PFOA) is a manufactured compound which persist in water and soil. The aim of the present study was to evaluate the possible changes in the thyroid gland of adult male albino rats after oral administration of PFOA. Material and methods: twenty male albino rats (150– 200 gm) and pathogenically free were obtained from Zagazig university. Animals divided randomly in to two groups, Group I (control) and Group II rat was PFOA and. Serum sample were collected for estimation thyroid hormones and thyroid gland samples were prepared for differ microscopic examination. Results: In our study, a significant decrease in the level of T3 and T4 with a significant increase of TSH in PFOA group compared to control group. . Thyroid gland sections in rats treated with PFOA showed a normal immunohistochemical expression of iNOS, while, in PFOA group showed a staining was stronger and the area of immunoexpression was greater in thyroid gland. Using Toluidine blue stain, thyroid gland sections in control group showed typical thyroid follicles lined with cuboidal epithelium and filled with homogeneous colloid and separated by capillary beds. However, PFOA group showed some follicles are distended with colloid, others appear collapsed. Mast cells in the interfollicular space with variable densities of the colloid staining. Conclusion: These findings suggest that oral dosing in rats with PFOA results in a noticed decrease in thyroid hormones and a structural change in thyroid tissues.