This study was carried out to investigate the effect of thyroidectomy on the histology of rat sublingual gland. Twenty-eight male Wistar albino rats, aged 4 weeks and weighing between 45-55 g, were used. The rats were divided into two experimental groups (control and thyroidectomy), each containing 14 animals. Total thyroidectomy of rats was performed under ether anesthesia in thyroidectomy group. The rats in the control group were sham operated without having the thyroidectomy. Seven rats randomly selected from both groups were fixed using the perfusion fixation technique 2 and 6 weeks after thyroidectomy, and their sublingual glands were harvested for histological investigation. No histological difference was observed between the two groups 2 weeks after thyroidectomy. However, 6 weeks after thyroidectomy considerable cytoplasmic vacuolization of the epithelial cells of the mucous tubules was seen in the thyroidectomy group compared to the controls. Enlargement of mucous tubules was also observed, and the lumina in most of the tubules was quite dilated. In the stroma surrounding the parenchymal tissues, increased lipid tissue mass was observed. In addition, increased connective tissue mass and mononuclear cell infiltrations were evident. Furthermore, the number of mast cells was significantly higher in the thyroidectomy group than in the controls 6 weeks after thyroidectomy. It was concluded that the thyroid gland and hormones might have an influence on the histology of the sublingual gland.