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Objectives: To investigate the effects of environmental tobacco smoke (ETS) on the inflammatory process of periodontitis by evaluating bone loss and the expression of cyclooxygenase-2 (COX-2) and Src homology phosphotyrosine phosphatase 2 (SHP-2)., Materials and Methods: Eighty 6-month-old male SD rats were randomized into four groups (10 rats/group/per time point): (a) normal group, (b) ETS group, (c) ligature-induced periodontitis group, and (d) ligature-induced periodontitis + ETS group. After treatment with ligature and/or ETS for 8 and 12 weeks, the levels of alveolar bone resorption and the expressions of COX-2 and SHP-2 in periodontal tissue were analyzed using histology and immunohistochemistry., Results: The ligature-induced periodontitis group displayed increased bone resorption and elevated expression of COX-2 and SHP-2 in periodontal tissues compared to the normal and ETS groups at 8 and 12 weeks. Furthermore, bone resorption and COX-2 and SHP-2 levels in the ligature-induced periodontitis + ETS group were significantly increased compared to those in the normal and ligature-induced periodontitis groups at both 8 and 12 weeks., Conclusion: Environmental tobacco smoke increased alveolar bone loss in periodontitis with enhanced expression of COX-2 and SHP-2 in periodontal tissues. Further investigation is needed to explore the role of COX-2 and SHP-2 in ETS-associated periodontitis., (© 2020 The Authors. Oral Diseases published by John Wiley & Sons Ltd.)