Chronic hepatitis is a major health problem that affects liver function with high morbidity and mortality in developing countries. Macerated pomegranate peel is utilized plant having high nutritional value. In our study we aimed to evaluate the hepatotherapeutic effect of pomegranate crude extract against CCl4-induced liver hepatitis in rats and to elucidate its underlying molecular mechanism through its effect on inflammatory biomarkers and liver function parameters changes. To achieve our objective a seventy five male albino rats was divided into 5 groups, normal healthy control group, hepatitis group, Silymarin protected group, hepatitis group treated with high conc. pomegranate extract, normal group with high conc. pomegranate extract. CCl4 caused a significant increase in the liver enzyme markers aminotransferases (AST, ALT) and ALP, γGT, A/G ratio, total bilirubin, direct bilirubin, and indirect bilirubin. Pomegranate extract cause a significant decrease with ALT, AST, ALP, total bilirubin, direct bilirubin and indirect bilirubin. Also, there were a slightly increase with serum total protein (TP) and Albumin. The relative gene expressions reflects the changes resulted in a significant increase with transcription levels genes IL-10, IL-1β, TNF-α, NFkB and Cox-2 with CCL4-induced chronic hepatitis rats after treatment by PE and a significant decrease with IL-10. Silymarin cause a significant increase with IL-1B, TNF-α, NFkB and Cox2 while, there was a significant decrease with IL-10. PE compared to silymarin showed an improvement in hepatoprotective, anti-inflammatory and antioxidant properties with chronic liver injury.