Lonicerae japonicae has shown antibacterial, anti-inflammatory, antipyretic, antioxidant, antiviral, and protective effects in animal models of chronic obstructive pulmonary disease. To investigate the effects of Flos L. japonicae (FLJ), a traditional Chinese medicinal herb, on acute lung inflammation induced by lipopolysaccharide (LPS), in vivo, using a murine model. Thirty 6-week-old female BALB/c mice were challenged with intratracheal LPS before treatment with FLJ or vehicle. FLJ was examined for its capacity to influence an LPS-induced increase in IL-10 and decrease in TNF-α, IL-1β and IL-6 as measured in murine bronchoalveolar lavage (BALF). FLJ increased nuclear Sp1 binding activity thereby enhancing the expression of IL-10 and decreased nuclear NF-κB binding activities thereby inhibiting the expression of TNF-α, IL-1β and IL-6 in the lung. The up-regulation of Sp1 activity by FLJ was through incremental phosphorylation of ERK. By contrast, the down-regulation of NF-κB activity by FLJ was through suppression of the phosphorylation of IκB, p38, and JNK. We demonstrated FLJ has protective activity against LPS-induced lung inflammatory cytokine release. Anti-inflammatory cytokine, IL-10, may prove beneficial in the treatment of endotoxin-associated lung inflammation. Display omitted