Background: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. Methods: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor ${alpha}$ (TNF-${alpha}$) and interleukin $1{eta}$ (IL-$1{eta}$) were measured in BALF. Nuclear factor ${kappa}B$ (NF-${kappa}B$), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. Results: TNF-${alpha}$ and IL-$1{eta}$ concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group ($5.5{pm}2.8$ nmol/mL vs. $16.5{pm}1.6$ nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group ($6.4{pm}1.8$ unit/g vs. $11.2{pm}6.3$ unit/g, tissue) (p<0.048). The concentration of NF-${kappa}B$ in NAC treatment group was significantly lower than that of LPS group ($0.3{pm}0.1;ng/{mu}L$ vs. $0.4{pm}0.2;ng/{mu}L$) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. Conclusion: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-${kappa}B$ activation.