Background and ObjectiveT and B cells are known to be involved in the disease process of periodontitis. However, the role of natural killer T cells in the pathogenesis of periodontitis has not been clarified.Materials and MethodsTo examine the role of these cells, C57BL/6J (wild‐type), CD1d−/− and α‐galactosylceramide (αGC)‐stimulated wild‐type mice were orally infected with Porphyromonas gingivalis strain W83.ResultsApart from CD1d−/− mice, the level of alveolar bone resorption was elevated by the infection and was further accelerated in αGC‐stimulated mice. The infection induced elevated levels of serum amyloid A and P. gingivalis‐specific IgG in the sera, although the degree of elevation was much smaller in the CD1d−/− mice. Infection‐induced RANKL elevation was only observed in αGC‐stimulated mice. Although the cytokines produced by splenocytes were mainly T‐helper 1 type in wild‐type mice, those in αGC‐stimulated mice were predominantly T‐helper 2 type. In the liver, the infection demonstrated no effect on the gene expression for interferon‐γ, interleukin‐4 and RANKL except αGC‐stimulated mice in which the infection upregulated the gene expressions.ConclusionThis study is the first to show that natural killer T cells upregulated systemic and local inflammatory responses induced by oral infection with P. gingivalis, thereby contributing to the progression of alveolar bone resorption.