Aim To study effects of N-Acetylcysteine on Lipopolysaccharide-induced immunological liver injury in mice. Methods A model of immunological liver injury was induced by injection of LPS in mice primed with BCG. NAC was administered in two different modes. In mode A, mice were pretreated with two doses of NAC before LPS, one (150 mg?kg-1, ip) at 4 h before LPS and the other (150 mg?kg-1, ip) at 15 min before LPS. In mode B, mice were administered with two doses of NAC after LPS, one (150 mg?kg-1, ip) injected immediately after LPS and the other (150 mg?kg-1, ip.) injected 4 h after LPS. Some mice were sacrificed at 1.5 h after LPS and livers were dissected for total RNA extraction. Hepatic TNF-? mRNA level was determined by using RT-PCR. The remaining mice were sacrificed at 8 h after LPS. Blood serum was collected for measurement of alanine aminotransferase (ALT) and nitrate plus nitrite. Livers were dissected for measurements of GSH and lipid peroxidation. Results Pretreatment with NAC significantly alleviated LPS-induced increase in ALT activity, attenuated LPS-induced hepatic GSH depletion and TNF-? mRNA expression in mice primed with BCG. However, NAC had no effects on LPS-induced NO production and hepatic lipid peroxidation. By contrastwith pretreatment, posttreatment with NAC had littleeffects on LPS-induced immunological liver injury and in fact aggravated LPS-induced NO production and hepatic GSH depletion and increased LPS-induced mortality in mice primed with BCG. Conclusion NAC has a dual effect on LPS-induced immunological liver injury. Pretreatment with NAC protects against LPS-induced immunological liver injury via counteracting LPS-induced oxidative stress and TNF-? mRNA expression in mouse liver. However, when administered after LPS, NAC behaves as a prooxidant and aggravates LPS-induced mortality in mice primed with BCG.