The effects of wogonin, a major flavonoid from Scutellaria baicalensis Georgi, on lipopolysaccharide (LPS)-induced lethal shock in mice was investigated. Wogonin pretreatment prevented the lethal shock in mice injected with D-galactosamine (D-GalN) and LPS, but not in mice injected with a high dose of LPS. Wogonin definitely inhibited the hepatic injury in mice injected with D-GalN, and LPS and reduced the level of circulating tumor necrosis factor (TNF)-alpha. The reduction was more marked in mice injected with D-GalN and LPS compared with that in mice injected with a high dose of LPS. Wogonin pretreatment did not inhibit the lipid peroxidation in mice receiving either D-GalN and LPS or a high dose of LPS. Wogonin inhibited the in vitro production of TNF-alpha and nitric oxide in LPS-stimulated RAW 264.7 cells. The mechanism of the protective effect of wogonin on the lethal shock in mice injected with D-GalN and LPS is discussed.