Objective To determine the effect of Nuclear factor-erythroid 2-related factor 2(Nrf2) on acute hephrotoxicity induced by CCl4 in male rat. Methods 20 male Wistar rats were randomly divided into control group and CCl₄ group, 10 rats in each group, another 10 male Wistar rats were transgenic rats microinjection through the carrier, obtained the Nrf2-tk gene integration and specific transgenic rats, as the CCl₄+Nrf2 integration group. The groups was given 1% polysorbate 80 for 4 days, Then the CCl₄ and CCl₄+Nrf2 integration group were intraperitoneally injected with a single dose of CCl₄ 7.5 mg·kg^-1 and were killed 24 h after CCl₄ injection. The serum chemical parameters including asparate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were measured. Also malonaldehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) levels in the liver as well as glutathione (GSH)/oxidized glutathione (GSSG) ratios were detected. Histopathologic changes in the liver were examined. Results F1generation TK transgenic rats in liver and testis and other tissues and organs were not detected the transcription of Nrf2-tk, indicating that Nrf2-tk expression in tissues is specific good. Nrf2 significantly reduced serum AST, ALT and LDH levels in a dose-dependent manner. The results of MDA levels and GSH/GSSG ratios in liver and kidney showed that Nrf2 reduced CCl₄ -induced hepatic lipid peroxidation, and ameliorated glutathione depletion. The histopathologic results showed that Nrf2 restrained liver and kidney damage induced by CCl₄. Conclusion Nrf2 can effectively protect male rat from acute hepatotoxicity and nephrotoxicity induced by CCl₄.