Regulatory effect of Toll-like receptor 4 (TLR4) gene on periodontitis in mice was investigated to explore its possible mechanism. Thirty C57/BL6 mice were randomly divided into the blank control group (N group, n=10), the periodontitis group (P group, n=10) and the periodontitis + TAK-242 group (PT group, n=10). The mice in P and PT group were ligatured with silk threads dipped with porphyromonas gingivalis (P. gingivalis) in the logarithmic phase to induce experimental periodontitis, and TAK-242 was intraperitoneally injected on the day when the periodontitis model was established. After fasting for 8 h, the expression levels of high-sensitivity C-reactive protein and inflammatory cytokines were measured in each group of mice. Their alveolar bones were isolated and changes were detected. Quantitative polymerase chain reaction was used to detect the expression levels of TLR4. After the mice were given TAK-242, the levels of hs-CPR, MCP-1, IL-6 and IL-1β in the PT group evidently increased (P<0.01) compared with those in the N group. After the mice were administered TAK-242, the alveolar bone density, the percentage of bone volume and the number of bone trabeculae in PT group were significantly reduced, and the bone trabecular space and structural model index were evidently decreased (P<0.01). In addition, the expression levels of and T-bet/GATA3 messenger ribonucleic acids (mRNAs) in peria of mice in the P group were significantly higher than those in the N group (P<0.01), whereas the expression level of Foxp3 mRNA was notably decreased (P<0.01). The involvement of TLR4 gene in the inflammatory response of periodontitis results in periodontitis, and its mechanism may be that it activates TLR4, so as to affect the expression of T-bet, GATA3 and Foxp3.