AIM: This study aimed to examine the effect of diabetes mellitus on the histology of parotid glands and to give a scientific overview of the distribution and the proliferative activity of myoepithelial cells (MECs) encircling both ducts and acini in parotid gland of both normal and diabetic mongrel dogs. MATERIALS AND METHODS: Twelve male mongrel dogs were used in the experiment and divided into two equal groups, group I, control group, group II, dogs with alloxan-induced diabetes. The dogs of the group II were injected by fresh preparation of a single dose of 100 mg/kg body weight of alloxan monohydrate dissolved in physiological saline. Ten days later, blood glucose level was determined using enzymatic colorimetric test; dogs presented a glucose level at or above 200 mg/dL were included in the diabetic group of the experiment. Three months later, dogs were sacrificed and the parotid glands from all groups were dissected and prepared for histological examination and double immunohistochemical expression of both actin and proliferating cell nuclear antigen (PCNA). RESULTS: Histological findings using H and E staining confirmed that the parotid gland parenchyma of the diabetic group had glandular atrophy characterized by loss of normal gland structure, acinar degeneration, and dilatation of the duct system with the presence of duct like structure. Moreover, there was a predominance of the fibrous component with the presence of fat cells within the gland compartments. Immunohistochemical findings of parotid gland of control group revealed positive scattered actin staining of weak to mild quantity in cells embracing some acini and intralobular ducts. Expression of PCNA in actin-positive cells revealed few scattered reactions embracing some acini and small ducts. Parotid gland of diabetic dogs revealed positive actin staining of mild-to-moderate quantity in the cells encircling the acini, intralobular, and some interlobular ducts. Expression of PCNA in actin- positive cells revealed mild-to-moderate positive reaction more concentrated in the cells surrounding both acini and intercalated ducts. CONCLUSION: Routine histological findings of diabetic dogs in our findings showed abundant pathological changes in parenchymal tissue elements, including acinar, ductal, and MECs that had a significant impact on saliva production and secretion resulting in dry mouth. The proliferative activity of MECs in the control group indicated a routine regeneration process, whereas the abundant proliferative activity in the diabetic group might indicate pathological transformation rather than regeneration, especially because no remedial measures were taken during this investigation.