This study sought to determine whether invariant NKT (iNKT) cells play an essential role in inflammation-induced preterm delivery. Preterm delivery and fetal death rates were determined in wild-type (WT) C57BL/6 mice and iNKT cell-deficient Jα18(-/-) mice injected i.p. with LPS. The percentages of decidual immune cells, including activated subsets, and costimulatory molecule expression were analyzed by flow cytometry. Th1 and Th2 cytokine production in the culture supernatants of decidual mononuclear cells was measured by ELISA. To some extent, Jα18(-/-) mice were resistant to LPS-induced preterm delivery. The proportions of decidual CD3(+) and CD49b(+) cells were slightly lower in Jα18(-/-) mice than in WT Jα18(+/+) mice, whereas almost no CD3(+)CD49b(+) cells could be found in Jα18-null mice. The percentages of activated decidual DCs, T cells, and NK cells were significantly lower in LPS-treated Jα18(-/-) mice than in WT mice. The CD40, CD80, and CD86 expression levels on decidual CD11c(+) cells from Jα18(-/-) mice were also significantly lower than in WT mice. Mean concentrations of Th1 cytokines IFN-γ and IL-12p70 in the culture supernatants of decidual mononuclear cells from LPS-treated Jα18(-/-) mice were apparently lower than those of LPS-induced WT mice. Additionally, the proportions of activated CD11c(+) cells, CD3(+) cells, and CD49b(+) cells in LPS-induced preterm delivery mice were strikingly higher in both WT and null mice when compared with the control PBS group and LPS-injected but normally delivered mice. Our results suggest that iNKT cells may play an essential role in inflammation-induced preterm birth.