Objective To investigate the protective effect of magnesium isoglycyrrhizinate( Mg IG) in rats with acute liver failure induced by D- galactosamine( D- Gal N) and related mechanisms. Methods A total of 90 Sprague- Dawley rats were randomly divided into normal group( group A,n = 10),model group( group B,n = 20),low- dose Mg IG group( group C,n = 20),medium- dose Mg IG group( group D,n = 20),and high- dose Mg IG group( group E,n = 20). The rats in group A received intraperitoneal injection of the same volume of normal saline,and those in the other groups received single intraperitoneal injection of 10% D- Gal N. At 30 minutes after establishment of the model,the rats in groups C,D,and E received tail vein injection of Mg IG injection( 25,50,and 100 mg / kg). At 24 and 48 hours after establishment of the model,HE staining was performed to observe the pathological changes in the liver,and serum was collected to measure the levels of liver function parameters [alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBil),and albumin( Alb) ],proinflammatory factors [tumor necrosis factor- α( TNFα),interleukin- 1β( IL- 1β),and interferon-γ( IFNγ) ],and anti- inflammatory factors [interleukin 4( IL- 4),interleukin- 10( IL- 10),and transforming growth factor β( TGFβ) ]in rats. The one- way analysis of variance was applied for comparison between multiple groups,and the Student- Newman-Keuls test was applied for comparison between any two groups. Results The serum levels of ALT,AST,TBil,and Alb showed significant differences across the five groups( F = 74. 6,108. 9,25. 1,and 58. 4,all P < 0. 05); compared with group A,group B had significant increases in the serum levels of ALT,AST,and TBil and a significant reduction in the serum level of Alb( all P < 0. 05); compared with group B,groups C,D,and E had significant reductions in the serum levels of ALT,AST,and TBil and a significant increase in the serum level of Alb,and these parameters showed the most significant changes in group E( all P < 0. 05). The serum levels of TNFα,IL- lβ,IFNγ,IL-4,IL- 10,and TGFβ showed significant differences across the five groups( F = 75. 1,58. 9,25. 4,43. 6,66. 4,and 86. 8,all P <0. 05); compared with group A,group B had significant increases in the serum levels of TNFα,IL- lβ,IFNγ,IL- 4,IL- 10,and TGFβ( all P < 0. 05); compared with group B,groups C,D,and E had significant reductions in the serum levels of TNFα,IL- lβ,and IFNγand significant increases in the serum levels of IL- 4,IL- 10,and TGFβ,and these parameters showed the most significant changes in group E( all P < 0. 05). Conclusion Mg IG can reduce inflammatory response through reducing proinflammatory factors and increasing anti- inflammatory factors,and thus exert protective effect on rats with ALF.