Scutellarin is a natural compound from a Chinese herb. The purpose of this paper was to study the protective effect of scutellarin on concanavalin A (Con A)-induced immunological liver injury and its effect on liver nuclear factor κB (NF-κB), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and inducible nitric oxide synthase (iNOS) expression in mice. Mouse liver injury was produced by injection of Con A 25 mg kg−1 via the tail vein. Scutellarin 50 or 100 mg kg−1 was peritoneally administered to mice 9 or 1 h before injection of Con A. The levels of serum alanine aminotransferase (ALT) and asparatate aminotransferase (AST), NO2−/NO3− and TNF-α were determined with biochemical kits, and ELISA using Quantikine Mouse TNF-α kit according the manufacturer's instructions. Liver lesions were examined by light microscope. The expression of TNF-α, IFN-γ, iNOS and Fas mRNA in the livers was detected by RT-PCR; and the expression of c-Fos, c-Jun, iNOS and IκB proteins was measured by Western Blotting. As a result, pretreatment with scutellarin 100 mg kg−1 significantly decreased the serum ALT, AST, NO2−/NO3−and TNF-α levels, and also reduced liver lesions induced by Con A. Scutellarin 100 mg kg−1 down-regulated expression of TNF-α and iNOS mRNA, and c-Fos, c-Jun and iNOS protein, while scutellarin enhanced the degradation of IκBα in the livers of mice injected with Con A. The results suggest that scutellarin has a protective action against Con A-induced liver injury in mice, and its active mechanism may be related to the inhibition of the NF-κB-TNF-α-iNOS transduction pathway.