Objective: To evaluate the ameliorator property of silymarin or/and Nigella sativa(N. sativa) extract against N-acetyl-p-aminophenol(APAP)-induced injury in male mice at the biochemical, histological and ultrastructural levels.Methods: The mice were divided into seven groups(10/group). The first group was served as control. While, the second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa extract alone respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa extract respectively. The seventh group was treated with combination of both ameliorative compounds(silymarin and N. sativa extract) with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose to mice led to an alteration of liver functions, increased the alanine transaminase, aspartate aminotransferase and lactate dehydrogenase levels, decreased total protein level as well as the increasing the superoxide dismutase and malondialdehyde while decreased catalase, glutathione peroxidase and glutathione reduced activities. The effects of APAP on the biochemical parameters of mice were dose-dependent. Administration of silymarin or/and N. sativa extract to APAP-treated mice attenuates the toxicity of this compound, objectified by biochemical, histological and ultrastructural improvement of liver. But the alleviation was more pronounced with the both antioxidants. Conclusions: The synergistic effect of silymarin and N. sativa extract is the most powerful in reducing the toxicity induced by APAP and improving the liver functions and antioxidant capacities of mice. Objective: To evaluate the ameliorator property of silymarin or / and Nigella sativa (N. sativa) extract against N-acetyl-p-aminophenol (APAP) -induced injury in male mice at the biochemical, histological and ultrastructural levels. Methods: The mice The first group was served with control of the control. While, the second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa extract alone respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa extract respectively. The seventh group was treated with combination of both ameliorative compounds (silymarin and N. sativa extract) with APAP and all animals were treated for a period of: 30 days. Results: Exposure to APAP at the treated dose to mice led to an alteration of liver functions, increased the alanine transaminase, aspartate aminotransferase and lactate dehydrogenase levels, decreased total protei n levels as well as the increasing the superoxide dismutase and malondialdehyde while decreased catalase, glutathione peroxidase and glutathione reduced activities. The effects of APAP on the biochemical parameters of mice were dose-dependent. -treated mice attenuates the toxicity of this compound, objectified by biochemical, histological and ultrastructural improvement of liver. But the alleviation was more pronounced with the both antioxidants. Conclusions: The synergistic effect of silymarin and N. sativa extract is the most powerful in reducing the toxicity induced by APAP and improving the liver functions and antioxidant capacities of mice.