The aim of the present study was to evaluate the effect of N-acetyl-l-cysteine (NAC) on bile duct ligation (BDL) induced oxidative stress in kidneys. Male Wistar rats were randomly segregated into four groups; sham control (SC), SC + NAC, BDL and BDL + NAC group. Liver damage was induced following BDL and renal injury was assessed by kidney function tests along with lipid peroxidation, nitrite levels, thiols and antioxidant enzymes. Three weeks after BDL, rats developed renal dysfunction in terms of elevated serum creatinine levels. BDL animals exhibited an increase in lipid peroxidation, reduction in thiols and redox ratio in liver and kidney tissue along with altered antioxidant enzymes in kidneys. BDL animals that were orally administered NAC at a daily dose 100 mg/kg for duration of two weeks, showed significant reduction in serum creatinine levels. NAC was effective in lowering lipid peroxidation and was able to restore thiol levels along with GSH/GSSG ratio in both liver and kidneys along with the activity of antioxidant enzymes in the kidneys of BDL animals. The results clearly demonstrate the efficacy of NAC in attenuating oxidative stress in kidneys, suggesting a therapeutic role for NAC in individuals with renal dysfunction following BDL.