Aim: Periodontitis is a chronic inflammatory disease characterized by tissue destruction. Patients with diabetes mellitus are moresusceptible to severe tissue destruction. Puerarin, a biological component derived from Pueraria lobate, has anti-inflammatory and anti-diabetic effects. The purpose of the study is to evaluate the protective role of puerarin on alveolar bone loss and connective tissue destruction in ligature induced diabetic and non-diabetic rats.Material and methods: Sixty rats were divided as non-diabetic control, non-diabetic-experimental periodontitis (EP)-systemic saline, non-diabetic-EP-systemic puerarin, diabetic control, diabetic-EP-systemic saline and diabetic-EP-systemic puerarin. Diabetes was induced by injection of streptozocin (200 mg/kg). EP was achieved by placing a sterile silk suture around the first molars into the gingival sulcus for 15 days. In puerarin treated groups, 200 mg/kg puerarin was applied daily for 15 days beginning one-day prior the placement of the ligature. The alveolar bone level of the first molar tooth, alveolar bone ratio in the furcation area and the attachment level were evaluated histologically. MMP-9, TIMP-1 levels and RANKL/OPG ratio were evaluated immunohistochemically.Results: Significantreduced alveolar bone and attachment losses were found in puerarin-treated groups comparing to in salineadministered groups (p<0.05). There was a significant reduction of RANKL/OPG ratio and MMP-9 levels and an increase in TIMP-1 levels in puerarin-treated groups compared with saline-administered groups during the induction of experimental periodontitis in both diabetic and non-diabetic condition (p<0.05).Conclusion: Puerarin might help to prevent alveolar bone loss and connective tissue destruction in periodontal disease in diabetic and non-diabetic condition.