The aim of this study was to investigate the possible effect of sex steroid deficiency on the mucosa of rat tongue as well as the influence of Tibolone. Methods: The tongue mucosa of ovariectomized rats (OVX) was compared to sham-operated rats by histology, immunohistochemistry and electron microscopy. The same evaluation was also performed after hormone replacement therapy. Results: The OVX animals demonstrated significant degenerative changes of tongue mucosa such as reduced thickness of epithelium with an irregular, significantly thinner keratinized surface. Partial disappearance of lingual papilla with irregular epithelial ridges were also noted. At ultrastructural level there were wide intercellular spaces, swollen and/or degenerated mitochondria, irregular dense nuclei, dilated perinuclear cisternae, cytoplasmic vacuolization and decreased tonofillament aggregations. The results from immunohistochemistry showed the possibility that the turnover period was prolonged in OVX rats. The degenerative changes of tongue mucosa were inhibited after administration of Tibolone. Conclusions: The overall results suggest that sex steroids have a specific role in the maintenance of normal tongue mucosa, and its deficiency deteriorates tongue mucosa ultrastructure and histology. Tibolone has a mild estrogenic action and has a good supportive effect on tongue structure.