The aim of this study was to evaluate the efficacy of the anti-inflammatory effects of propolis on the systemic and local effects on experimental periodontitis and diabetes. Fifty-six Wistar rats were divided into seven groups: (1) negative-control (NC), (2) periodontitis (P), (3) diabetes (D), (4) diabetes+periodontitis (DP), (5) periodontitis+propolis (P-Pro), (6) diabetes+propolis (D-Pro), and (7) diabetes+periodontitis+propolis (DP-Pro). Periodontitis was induced by ligature placement and diabetes was induced by streptozotocin injection. Propolis (Pro) was administrated by oral gavage (100 mg/kg/day). On day 21, plasma was obtained for analysis and alveolar bone level was evaluated using histomorphometric analysis. Compared to NC the final blood glucose levels for D-Pro was not significantly different (P=.052), however, D, DP, and DP-Pro were significantly different. There were no statistically significant differences in blood glucose concentrations between P and P-Pro, between D and D-Pro, and between DP and DP-Pro. All groups showed significantly more alveolar bone loss compared with NC. A significant difference in bone loss was found between P and P-Pro, and DP and DP-Pro, however there was no difference between D and D-Pro. Plasma interleukin 1beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinase-8 (MMP-8) levels were not significantly different among groups. In conclusion, propolis reduced fasting blood glucose levels in diabetes. In addition, propolis might be beneficial as an adjunct treatment of diabetes associated periodontitis and periodontitis without diabetes.