Structural changes in parotid gland (PG) were previously reported following ablation of thyroid gland. However, the functional alterations (especially for proteins) have not been elucidated yet. Herein, we investigated the effect of rat thyroidectomy on PG structure and protein content and studied the ability of thyroxin-supplementation to alleviate the associated structural and functional changes. Male young adult 4-month old albino rats (n=48) were allocated equally into 4 groups (control, sham-operated, thyroidectomized, and thyroxinsupplemented). PGs were examined histologically, and their proteins expression and localization were analyzed using western blot (WB) and immunohistochemistry (IHC), respectively at 3 w and 5 w post-surgery. Functionally, PGs of thyroidectomized rats formed a newly expressed 300 KDa protein, which was confirmed to be thyroglobulin (TG) by WB and IHC, with higher expression at 5 w. TG was localized in the interstitium, within capillaries, in the cytoplasm of the intralobular ductal cells, in the secretory products within the ductal lumen, and in the cytoplasm of individual small cells at the periphery of the acini. This functional change accompanied by structural changes in PGs (presence of dark and light acinar cells, TG-like colloid material, and high periductal vasculature). Noteworthy, PG of the thyroxin-supplemented depicted vanishment of TG. From these data, it could be concluded that thyroidectomy could alter the morphology and function of the parotid that induce a thyroid-like reprogramming of the parotid to secrete TG and thyroxin supplementation could alleviate this effect.