Several studies have examined the deleterious effects of diabetes on the oral mucosa. In this study, we examined the histological, ultrastructural and stereological changes in the oral epithelium of diabetic NOD mice and correlated the findings with the processes of tissue repair, healing and susceptibility to infection. Twenty-seven female mice were allocated to one of three experimental groups (n= 9/ group) BALB/c control mice, non-diabetic NOD mice and diabetic NOD mice. After confirmation of the diabetic state based on the urine glucose levels, tissue samples were collected from the cheek mucosa and processed for light and transmission electron microscopy. Diabetic NOD mice showed atrophy of the oral epithelium with definite cellular polymorphism and indistinguishable cell layers. The alterations seen included a reduced number of cell organelles, cell membrane disorganization, the accumulation of lipid droplets in the cell cytoplasm, an increased intercellular space and slight superficial desquamation. Non-diabetic NOD mice showed only moderate morphological alterations in the cheek mucosa. These results indicate that diabetes adversely affects the morphology of the cheek mucosa, which may compromise tissue function to favor the occurrence of oral infections.