In recent years, important advances have occurred in the determination of diagnostic criteria for the disease diabetes mellitus and in new strategies for its treatment. The purpose of this research was to develop a new method for diabetes diagnosis by microscopic and cytomorphometric analyses of the oral epithelium. The smears were obtained from three distinct oral sites: buccal mucosa (cheek), tongue dorsum, and floor of the mouth in 10 control individuals and 10 type II diabetic patients. The oral smears were stained with Papanicolaou EA-36 solution. The nuclear (NA) and cytoplasmic (CA) areas were evaluated from 50 integral cells predominant in each oral site by the use of the KS 300 image analysis system (Carl Zeiss, Germany), by which the cytoplasmic/nuclear ratio (C/N) was calculated. The results showed that: (i) the epithelial cells of the diabetic group exhibited figures of binucleation and occasional karyorrhexis in all layers; (ii) the NA was markedly higher (P < 0.05) in the diabetic group; (iii) the CA did not exhibit a statistically significant difference (P > 0.05) between these two groups; and (iv) the C/N mean was 37.4% lower in the type II diabetic group. These results associated with clinical observations suggest that diabetes mellitus can produce alterations in oral epithelial cells, detectable by microscopy and cytomorphometry, which can be used in the diagnosis of this disease.