Objective:To investigate the possible mechanism of San-Cao Granule (SCG,三草颗粒) mediating anti liver fibrosis.Methods:A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group,porcine serum-treated group,ursodesoxycholic acid (UDCA,60 mg/kg),SCG (3.6 g/kg) group,SCG (1.8 g/kg) group and SCG (0.9 g/kg) group,with 10 rats in each group.Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks,except for the normal control group.Then,the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks.The serum levels of alanine transaminase (ALT),aspartate transaminase (AST),albumin (ALB),total bilirubin (TBIL),hyaluronic acid (HA),laminin (LN),and type Ⅳ collagen (ⅣC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining.Moreover,the protein expression levels of high mobility group box-1 protein (HMGB1),transforming growth factor β 1 (TrGF-β 1),phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3),Smad7,toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MyD88),nuclear factor-kappa B (NF-κ B) and α-smooth muscle actin (α-SMA) were determined by westem blot,immunohistochemistry and real time quantitativereverse transcription polymerase.Results:Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT,AST,TBIL,HA,LN and ⅣC and preventing the serum level reducing of ALB compared with the model group (all P＜0.01).Meanwhile,the collagen deposition was attenuated by SCG and UDCA treatment.Furthermore,SCG markedly reduced the expressions of HMGB1,TGF-β 1,p-Smad3,TLR4,MyD88,NF-κ B and α-SMA,and enhanced the expression of the Smad7 compared with the model group (all P＜0.01).Conclusion:SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1,TLR4/NF-κ B and TGF-β 1/Smad signaling pathway.