Background: One of the safest antipyretics, analgesics is paracetamol when used at therapeutic doses but overdoses caused hepatic necrosis. Recent researches were proven the ability of pomegranate to treat many diseases. For new ways to reduce paracetamol toxicity pomegranate peel extract was used in comparison to N- Acetyl cysteine a standard antidote for paracetamol toxicity. Methods: Seventy two adult male albino rats were divided equally into nine groups; Negative control group; Solvent )distilled water) group; N-Acetyl cysteine treated group (a single dose 150 mg/kg. B.w/day orally); Pomegranate peel extract treated group (a single dose 430mg/kg. b. W/ day orally); N-Acetyl cysteine and Pomegranate peel extract treated group (each rat was given same previous doses); Paracetamol group (a single dose of 400 mg/ kg. B.w / day orally); N-Acetyl cysteine; Pomegranate peel extract and combination of N-Acetyl cysteine and Pomegranate peel extract with paracetamol were three treatment groups received the same previous doses. Treatment Continued for 28 days. These samples were collected for matrix metalloproteinase assessment in blood serum; Hepatic antioxidants and Oxidative stress marker assessment in plasma and liver tissue homogenates and Routine liver injury marker assessment in blood serum. Res49ults: Treatment with paracetamol caused hepatic toxicity, the Pomegranate peel extract showed a mild hepatoprotective effect, N-acetyl cysteine showed the moderate hepatoprotective effect and combination treatment of N-Acetyl cysteine and Pomegranate peel extract showed the best hepatoprotective effect against paracetamol toxicity. Conclusion: Paracetamol is a hepatotoxic and combination of N-Acetyl cysteine and the Pomegranate peel extract is the best treatment against Paracetamol hepatic toxicity.