This study was conducted to investigate the biochemical effects of Paracetamol which chemically named as N-acetyl-p-aminophenol (APAP) high dose on experimental animals and to study the anti-inflammatory, immunomodulatory, antioxidant and hepatoprotective activity of oil (ethanolic) and aqueous (water) extracts of Moringa oleifera (M. oleifera)  leaves supplementation as well as choosing the best extract. This study was carried out on eighty three male adult albino rats of Sprague-Dawely strains which were divided into eight groups, of ten animals each except APAP control group were composed of thirteen rats, all rats were fed commercial diet. Group (I): rats received a placebo 1g of 0.9% normal saline by oral intubation daily, while other groups received a high dose of APAP (1g APAP/kg body weight) daily by oral intubation to induce hepatotoxicity. Group (II): rats received APAP dose daily without any treatments. Groups (III, IV and V): rats received APAP dose and supplemented with water extract of M.olifera at three tested doses (200,300 and 400mg/Kg body weight) respectively daily by oral intubation. While groups (VI, VII and VIII), rats received APAP dose and supplemented with ethanolic extracts of M.olifera at three tested doses (200,300 and 400mg /Kg body weight) respectively daily for four weeks.     At the end of the experimental period (four weeks) rats were anesthetized using diethyl ether anesthesia after overnight fasting. Blood samples were collected from the hepatic portal vein and serum was separated for analysis. Then rats sacrificed and abdomen was opened at greater curvature as liver and spleen were removed for biochemical and microscopical examination.     The present study showed that APAP administration caused a significant increase in the level of hepatic protein carbonyl group (PCG), malondialdehyde (MDA) and nitric oxide (NO) levels. On the other hand, reduced blood glutathione (GSH) level, serum catalase (CAT), glutathione-S-transferase (GST), and glutathione reductase (GR) activities as well as serum immunoglobulins (IgG and IgM) levels were significantly decreased compared to healthy control group at (p≤0.05). The inflammatory markers like serum tumor necrosis factor  alpha (TNF- α), interleukin 1 beta (IL1b) levels and myeloperoxidase (MPO) activity                              Corresponding author:Sayed_abdrahman@yahoo.com increased in APAP control group. The study revealed the toxic effect of APAP on the liver function enzymes asserum- glutamyltransferase (GT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities were significantly increased in APAP control group compared to healthy control group at (p≤0.05).  Administration of water or ethanolic extracts at the tested doses (200,300 and 400mg/Kg body weight of rats) daily resulted in a significant decrease in oxidative biomarkers, inflammatory markers, liver function enzymes activities and significant improvement in antioxidants levels and the immune function as compared with APAP hepatotoxicated rats at (p≤0.05).Results of this study suggested that ethanolic extracts were more effective and the highest improvements were found in group which treated with the highest dose of the ethanolic extract (400mg/kg body weight).