[Objective] The oral cavity is a first barrier toward the entry of bacteria and viruses into the body. In this study, we investigated the role of toll-like receptors (TLRs) in the submandibular gland (SMG) during the host defense against LPS, as the saliva is mostly secreted from the SMG. [Materials and Methods] TLR4-mutant and it's wild type mice (C3H/HeJ and C3H/HeN, respectively) were used; RT-PCR, immunohistochemistry, and Western blotting were employed to investigate the expression of inflammation cytokines. [Results and Discussion] In the SMG of C3H/HeN mice, mRNAs for TNF-α and IL-1β were strongly induced by LPS injection (i.p). Induction of these cytokines was transient, being maximum at around 6 h after injection. These inflammation cytokines were not induced in C3H/HeJ mice. Denervation of the superior cervical trunk and chorda tympani nerve did not diminish the LPS-induced elevation of IL-1β mRNA in submandibular gland, indicating the irrelevance of the central nervous system in this induction. In addition, TLR4 mRNA was shown to be strongly expressed in the SMG. These facts suggest that TLR4 is involved in the induction. The IL-1β protein was detected in the SMG of C3H/HeN mice, and it localized in the secretary granules present in the granular convoluted tubular cells. The IL-1β protein was secreted into saliva and its level was increased by LPS injection. The present study suggest that one of inflammation cytokines, IL-1β is induced and secreted into saliva in response to the inflammation happens in the local sites including the oral cavity. [Jpn J Physiol 54 Suppl:S73 (2004)]