OBJECTIVE: To investigate the histopathological alterations in gingival tissue of streptozotocin (STZ) diabetic rats and the expressions of ADAMTS-5 and TNF-α to better understand the effects of diabetes on oral mucosa. STUDY DESIGN: Twenty Wistar rats, divided into control and diabetic groups, received a single dose of STZ (55 mg/kg) ip. The rats were sacrificed, and gingival tissues were dissected and fixed in formalin for routine paraffin protocol. Hematoxylin-eosin and immunohistochemical staining (ADAMTS-5 and TNF-α) were applied and sections were examined under a microscope. RESULTS: The control group revealed regular placement of epithelial cells. In the diabetic group significant thinning of the epithelial cell layer, degeneration of the cells in the papillary region, pyknosis in nuclei, and inflammatory cell infiltration were seen. Negative ADAMTS-5 expression was observed in parakeratinized epithelium of the control group. The diabetic group showed positive ADAMTS-5 expression in the epithelial cells. In the control group, TNF-α positive expression was observed in some of the gingival epithelial and vascular endothelial cells. In the diabetic group, TNF-α expression was observed in basal lamina, endothelial cells, and fibroblast cells and dilated blood vessels. CONCLUSION: In diabetics, hypertrophic changes of the gingival epithelium with the epithelial permeability alteration and the presence of intraepithelial inflammatory cells eventually gave rise to degenerative lesions and epithelial ulceration. © Science Printers and Publishers, Inc.