Background: The aim of this study is to characterize and evaluate the host response caused by three different models of experimental periodontitis in mice.Methods: C57BL/6 wild-type female mice were distributed into six experimental groups and sacrificed at 7, 15, and 30 days after the induction of periodontal disease: 1) group C: no treatment control group; 2) group L: periodontal disease induced by ligature; 3) group G-Pg: oral gavage with Porphyromonas gingivalis (Pg); 4) group G-PgFn: oral gavage with Fusobacterium nucleatum + Pg; 5) group I-Pg: heat-killed Pg injected into the palatal mucosa between the molars; and 6) group I-V: phosphatebuffered saline injected into the palatal mucosa. The samples were used to analyze the immune-inflammatory process in the gingival tissue via descriptive histologic and real-time polymerase chain reaction analyses. The alveolar bone loss was evaluated using microcomputed tomography. The data were analyzed using the Kruskal-Wallis test, followed by a post hoc Dunn test and analysis of variance, followed by a Tukey test using a 5% significance level.Results: Only the ligature model displayed significant alveolar bone loss in the initial period (7 days), which was maintained with time. The group injected with heat-killed Pg displayed significant alveolar bone loss starting from day 15, which continued to progress with time (P