Objective: The goal of this study was to evaluate effect of mechanical stress under denture base on palatal tissue in xerostomia model rats. Methods: Eighty 10-week-old male rats were divided into four groups; normal [N], normal + mechanical stress [NS], xerostomia [X], xerostomia + mechanical stress [XS]. The group X and XS underwent sialadenectomy of the submandibular and sublingual glands and ligation of the paratid ducts bilaterally. Seven weeks after the operation, an apparatus which exerted the mechanical stress to the palatal mucosa by mastication was fixed to the upper molar region of the rat in the group NS and XS. After 1, 3, 7 and 14 day(s), five rats from each group were sacrificed and the palatal tissue blocks were excised. The specimens were fixed in formalin and embedded in paraffin wax. Haematoxylin-Eosin staining and argyrophilic nucleolar organizer regions (AgNORs) staining were performed on the sections (4µm). The histopathological changes were studied under light microscope and AgNORs dots in the mucosal epithelium were counted. These parameters were compared among the groups and analyzed statistically (p<0.05, One-factor ANOVA and Scheffé test). Results: No histopathological changes were observed throughout the observation period in the group N and X. In the group NS, bone resorption was observed after 3, 7 and 14 days. In the group XS, severe bone resorption was observed throughout the observation period. A significant decrease in AgNORs count was found in the group NS (1.36±0.26) and XS (1.28±0.13) compared with the group N (1.98±0.16) and X (1.78±0.15). The AgNORs count in the group NS tended to increase after 14 days. In the group XS, no change in AgNORs count was found throughout the observation period. Conclusion: Xerostomia caused severe damage by the mechanical stress on the palatal tissue and prolonged the healing of the palatal mucosa in rats.