OBJECTIVES: Diabetes mellitus (DM) is well-established risk factor for periodontal disease. DM can also lead to changes in the number of apoptotic cells in periodontal tissues. The goal of this study was to evaluate apoptosis, depending on DM, in healthy and diseased periodontal soft tissues. MATERIAL AND METHODS: A total of 43 adult male Sprague-Dawley rats were used in this study. Experimental periodontitis was created by placing silk ligatures around the cervices of the first mandibular molars. Experimental diabetes was induced by intraperitoneal injection of the diabetogenic agent streptozotocin (STZ). Following the induction of both experimental diseases, the animals were divided into four groups: (1) The healthy group (H) (n = 10); (2) The diabetes group (D) (n = 10); (3) The periodontitis group (P) (n = 11); and (4) The diabetes and periodontitis group (DP) (n = 12). Apoptotic cells were determined by immunohistochemistry, and the frequency of apoptotic cells was evaluated by apoptotic index score. RESULTS: It was observed that there was less apoptosis in both the epithelial and gingival connective tissue cells of healthy diabetic tissues than in healthy tissues without diabetes. When periodontal disease existed, apoptosis increased in both the epithelial and gingival connective tissues of diabetic and non-diabetic animals. CONCLUSIONS: There may be differences in the apoptotic mechanisms in the periodontal soft tissues of diabetic and non-diabetic animals. CLINICAL RELEVANCE: Apoptosis may be one of the underlying factors in increased risk for periodontal disease that is associated with diabetes.