Abstract: Objective To investigate protective effect and mechanism of α-lipoic acid on liver disease and hepatic fibrosis in diabetic rats.Methods The Sprague-Dawley rats were randomly divided into 5 groups:normal control group(n=10),model group of diabetic liver disease induced by streptozotocin(60 mg/kg) intraperitoneal injection+tetrachloride carbon(n=8),low-dose α-lipoic acid group(15 mg/kg·d intragastirc administration for 12 weeks,n=9),medium-dose α-lipoic acid group(30 mg/kg·d intragastirc administration for 12 weeks,n=9),and high-dose α-lipoic acid group(60 mg/kg·d intragastirc administration for 12 weeks,n=9).Levels of malondialdehyde,glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and blood glucose in blood and liver tissue of the rats were measured.Expression of matrix metalloproteinase 9(MMP-9) and tissue inhibitor of metalloproteinase factor-1(TIMP-1) protein expression were determined with immunohistochemistry and western blot.Results Compared with the normal control group,blood glucose(25.45±3.24 mmol/L) and malondialdehyde(11.90±3.38 ug/mg·pro) were increased,while SOD(38.45±6.73 mmol/L),GSH-Px(19.54±2.24 mmol/L),MMP-9,TIMP-1,and MMP-9/TIMP-1 were reduced(P<0.01 for all).Compared with the model group,blood glucose(14.25±3.23 mmol/L) and malondialdehyde(8.05±2.13 mmol/L) of medium-dose α -lipoic acid group were reduced(P<0.01),and SOD(46.95±6.13 mmol/L),GSH(25.14±3.23 mmol/L),MMP-9,TIMP-1,and MMP-9/TIMP-1 were increased(P<0.01 for all).Conclusion The study shows that α-lipoic acid has protective effect on liver tissue of diebetic rat.The mechanism probably relates to the reduce of oxide stress,attenuation of extracellular matrix,and inhibition of liver fibrosis.