Potassium dichromate is widely used in various laboratory and industrial applications. Vitamin C and melatonin are well-known antioxidants. Study the microscopic and morphometric alterations in the thyroid gland in adult male albino rats after the administration of potassium dichromate for successive 2 months and also to assess the possible protective effect of vitamin C versus melatonin on these changes. Sixty adult male albino rats were randomly divided into four main groups. Group I (The control group). Group II received potassium dichromate (25 mg/kg/day) dissolved in distilled water by intraperitoneal (i.p) injection for 2 months. Group III received the same dose of potassium dichromate with vitamin C (120 mg/kg/day) orally through an intragastric intubation. Group IV received the same dose of potassium dichromate and melatonin (10 mg/kg/day) as an i.p injection. Thyroid gland samples were prepared for light and electron microscopic studies. Potassium dichromate group demonstrated congested blood vessels, follicular hyperplasia, follicular enlargement with degenerated lining cells that were exfoliated in the lumen. The parafollicular cells appeared with darkly stained nuclei. PAS reaction showed weak reaction in the colloid with an abnormal pattern of vacuolization. A highly significant increase in the percentage area of fibrosis was detected in Mallory trichrome sections. Ultrastructurally, follicular cells and parafollicular cells appeared irregular in shape with dark, small heterochromatic nuclei. Small, electron-dense granules in the parafollicular cells were found. Potassium dichromate and vitamin C-treated group III showed partial improvement of the thyroid gland. The PAS reaction showed that nearly all the follicles were more or less similar to those of the control group. A significant decrease in the percentage area of fibrosis in group III was found as compared to those in group II. Potassium dichromate and melatonin-treated group showed that the thyroid gland was nearly similar to that of the control group. Vitamin C and melatonin could partially protect against potassium dichromate induced changes in the thyroid gland and the protective effect of melatonin was better than that of vitamin C.