ETHNOPHARMACOLOGICAL RELEVANCE: Cichorum glandulosum Boiss. et Huet is a traditional Uygur herbal medicine that has been used as a cholagogic and diuretic agent to improve liver function. However, the mechanism is not known for the liver-protective function. We investigated the antioxidant effects of plant extraction (CGE60) in vitro and in vivo, and find the mechanism of liver protection in Bacille Calmette-Guerin vaccine (BCG)+Lipopolysaccharides (LPS) induced liver injury in mice. MATERIALS AND METHODS: CGE60 was made, and the antioxidant activity was investigated by comparing the ability of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2-azinobis(3-ehtylbenzothiazolin-6-sulfnicAcid) diammonium salt (ABTS) free radicals in vitro. Then, CGE60 was administrated in mice of liver damage model which was induced in mice using the BCG+LPS protocol. The CGE 60 extract was tested at three dosages: 50 mg/kg, 100 mg/kg, and 200 mg/kg. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX,), nitric oxide (NO), nitric oxide synthetase (NOS), hydroxyproline and alkaline phosphatase (ALP) contents were evaluated in liver to determine the CGE60 activity in the hepatic injury model. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) proteins were determined in the liver tissues using ELSIA. The signaling activities were evaluated in Western blot. RESULTS: CGE60 exhibited strong antioxidant ability in vitro. With oral administration, CGE60 significantly increased the activity of CAT, SOD, GSH-PX, and decreased the level of NO, NO synthase, hydroxyproline, ALP and lipid peroxidation liver of in the BDG+ LPS model. CGE60 attenuated hepatic inflammation via down- regulation of TNF-α, IL-6 and TGF-β. CGE60 blocked protein expression of cytochrome P450 2E1 (CYP2E1), nuclear factor kappa-B (NF-κB), phosphorylation of extracellular signal-regulated kinase (p-ERK1/2), and cyclooxygenase-2 (COX-2),but activated the expression of p-P38 MAPK. CONCLUSION: This study suggests that CGE60 possesses antioxidant activity and this activity associates with hepatoprotective effect in the mice of BCG +LPS model, and the mechanisms underlying these effects may involve antioxidant actions and anti-inflammation activities.