Aim: The aim of the present study was to investigate the therapeutic and preventive effects of N-acetyl cysteine and erdosteine on renal injury associated with paracetamol (acetaminophen) intoxication. Materials and methods: Female albino Wistar rats were divided into six groups: control; paracetamol (1 g/kg, oral); paracetamol (1 g/kg, oral) + erdosteine (150 mg/kg/day, oral); paracetamol (1 g/kg, oral) + N-acetyl cysteine (140 mg/kg bolus, followed by 70 mg/kg, oral); N-acetyl cysteine control (140 mg/kg bolus, followed by 70 mg/kg, oral); and erdosteine control (150 mg/kg/day, oral). Potential renal injury was assessed using biochemical analyses, radionuclide imaging, and histopathological parameters. Results: In the paracetamol group, blood urea nitrogen and creatinine levels were significantly increased compared with controls. Histopathological examination showed tubular vacuolization, tubular necrosis, and remarkable interstitial inflammation. The excretion function was observed to be insufficient on radionuclide imaging. However, in the groups treated with erdosteine or N-acetyl cysteine after paracetamol, biochemical analyses, radionuclide imaging, and histopathological parameters showed significantly less evidence of renal toxicity than that observed in the group receiving paracetamol alone. Less renal toxicity was detected in rats receiving N-acetyl cysteine than in those receiving erdosteine. Conclusion: Renal injury may develop after paracetamol overdose. Erdosteine and N-acetyl cysteine are both effective in the prevention of renal injury when given in the early phase of paracetamol nephrotoxicity. N-acetyl cysteine is more protective than erdosteine.