Abstract: AIM To study the effect of leflunomide (Lef) on immunological liver injury in mice. METHODS Immunological liver injury was induced by tail vein injection of BCG+LPS (BCG 2.5 mg, 1 d, LPS 10 μg, 10 d). The ALT, AST, NO level in plasma and MDA, GSHpx in liver homogenate were assayed by spectroscopy. The serum content of TNF-α was determined by ELISA. IL-1, IL-2 and ConA-induced splenocyte proliferation response were determined by methods of ³H infiltrated cell proliferation. RESULTS Immunological liver injury induced by BCG+LPS was successfully duplicated. Lef (4, 12, 36 mg·kg^-1) was found to significantly decrease the serum transaminase (ALT, AST) activity and MDA content in liver homogenate, and improved reduced GSHpx level of liver homogenate. Furthermore, Lef (4, 12, 36 mg·kg^-1) significantly reduced TNF-α and NO level in serum, and IL-1 production by PM_Ф. Moreover, the decreased IL-2 production and ConA-induced splenocyte proliferation response were further inhibited. CONCLUSION Lef showed significant protective action on immunological liver injury in mice.