Lanthanide ions have been proven to have various biologic effects. Lanthanum with extremely active physical and chemical property was evidenced to possess antibacterial and immune adjustment effects. In the present study, the anti-inflammatory effects of lanthanum chloride (LaCl(3)) on lipopolysaccharide (LPS)-challenged mice were examined in vivo and in vitro. The results indicated that LaCl(3) can greatly decrease the secretion of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β as well as TNF-α mRNA expression in the mice challenged with LPS. To clarify the mechanism involved, the effects of LaCl(3) on the activation of nuclear factor (NF)-κB were examined both in liver and in peritoneal macrophages. The LPS-induced activation of NF-κB was significantly blocked by LaCl(3). These findings demonstrate that the inhibition of the LPS-induced inflammatory media, such as TNF-α and IL-1β, by LaCl(3), is due to the inhibition of NF-κ B activation.