Diabetes Mellitus (DM) is a syndrome accompanied with the abnormal secretion or function of insulin, a hormone that plays a vital role in controlling the blood glucose level (BGL). Type 1and 2 DM are most common form and the prevalence of the latter is recently increasing. The aim of this article was to assess whether Type 2 DM could act as a predisposing risk factor on the pulpo-periapical pathogenesis. Previous literature on the pathologic changes of blood vessels in DM was thoroughly reviewed. Furthermore, a histopathologic analysis of artificially-induced periapical specimens obtained from Type 2 diabetic and DM-resistant rats was compared. Histopathologic results demonstrate that the size of periapical bone destruction was larger and the degree of pulpal inflammation was more severe in diabetic rats, indicating that Type 2 DM itself can be a predisposing risk factor that makes the host more susceptible to pulpal infection. The possible reasons may be that in diabetic state the lumen of pulpal blood vessels are thickened by atheromatous deposits, and microcirculation is hindered. The function of polymorphonuclear leukocyte is also impaired and the migration of immune cells is blocked, leading to increased chance of pulpal infection. Also, lack of collateral circulation of pulpal blood vessels makes the pulp more susceptible to infection. These decrease the regeneration capacity of pulpal cells or tissues, delaying the healing process. Therefore, when restorative treatment is needed in Type 2 DM patients, dentists should minimize irritation to the pulpal tissue un der control of BGL.