Peri-implantitis and periodontitis are different entities in immune characteristics even though they share similar features in clinical and radiologic signs. Toll-like receptor 2 (TLR-2), one of the key pathogen-recognition receptors in the innate immune system, plays an important role in the progression of periodontitis. However, the role of TLR-2 in peri-implantitis remains unclear. The objective of this study was to investigate the role of TLR-2 in inflammation and alveolar bone loss in a murine model of ligature-induced peri-implantitis and to compare it with ligature-induced periodontitis. Smooth-surface titanium implants were placed in the alveolar bone of the left maxillary molars of wild-type (WT) and Tlr2 knockout (Tlr2-KO) mice 6 weeks after tooth extraction. Silk ligatures were applied to the left implant fixtures and the right maxillary second molars to induce peri-implantitis and periodontitis 4 weeks after implant placement. Two weeks after ligation, bone loss around the implants and maxillary second molars was analysed by micro-computed tomography (micro-CT), and inflammation around the implants and maxillary second molars was assessed at the same time point using histology and TRAP staining, respectively. Expression of mRNA for proinflammatory cytokines (interleukin-1β [Il1β], tumor necrosis factor-α [Tnfα]), an anti-inflammatory cytokine (interleukin-10 [Il10]) and osteoclastogenesis-related cytokines (Rankl, osteoprotegerin [Opg]) were evaluated, in gingival tissue, using real-time quantitative PCR (RT-qPCR). The success rate of implant osseointegration was significantly higher in Tlr2-KO mice (85.71%) compared with WT mice (53.66%) (P = .0125). Micro-CT revealed significantly decreased bone loss in Tlr2-KO mice compared with WT mice (P = .0094) in peri-implantitis. The levels of mRNA for Il1β (P = .0055), Tnfα (P = .01) and Il10 (P = .0019) in gingiva were significantly elevated in the peri-implantitis tissues of WT mice, but not in Tlr2-KO mice, compared with controls. However, the gingival mRNA ratios of Rankl/Opg in peri-implant tissues were significantly upregulated in both WT (P = .0488) and Tlr2-KO (P = .0314) mice. Ligature-induced periodontitis exhibited similar patterns of bone loss and inflammatory cytokine profile in both groups of mice, except that the level of Il10 was elevated (P = .0114) whereas the Rankl/Opg ratio was not elevated (P = .9755) in Tlr2-KO mice compared with control mice. Histological findings showed increased numbers of TRAP-positive cells and infiltrated inflammatory cells in ligature-induced peri-implantitis in both WT (P < .01) and Tlr2-KO mice (P < .05), and the numbers of both types of cell were significantly higher in WT mice than in Tlr2-KO mice (P < .01). This study suggests that TLR-2 mediates bone loss in both peri-implantitis and periodontitis. However, different molecular features may exist in the pathogenesis of the two diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.