Introduction: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, the main pharmacologically active component of Salvia miltiorrhiza. The aim of this study was to investigate the effect of STS on concanavalin A (ConA)-induced hepatitis (CIH) in mice, an experimental model of immune-mediated liver injury. Results: C57BL/6 mice pretreated with STS released much less alanine transaminase into plasma in response to ConA challenge and had reduced inflammatory infiltration and hepatocyte apoptosis in the liver compared with control mice pretreated with vehicle solutions. Thus, STS protected mice from CIH. In STS-pretreated mice induced with CIH, we found abrogated tumor necrosis factor-α and interferon (IFN)-γ production. Moreover, mRNA expressions of IFN-inducible protein-10 and macrophage inflammatory protein-1α in these mice were decreased. The mechanism of anti-inflammatory effects of STS may be attributed to its modulation of crucial inflammatory signaling pathways, including NF-κB and IFN-γ/STAT1. Conclusion: In conclusion, STS was capable of protecting mice from immune-mediated liver injury in vivo, and the protection was associated with its suppressive effect on the production of important inflammatory mediators through modulating NF-κB and IFN-γ/STAT1 signaling pathways. © 2008 Springer Science+Business Media, LLC.