Acetaminophen (APAP) or paracetamol is a widely prescribed analgesic and antipyretic drug either as a single compound or in combination with other medications (Kaplowitz 2004). Excessive use of APAP can damage the liver and if not treated, overdose can lead to liver failure (Larson et al 2005). Beta carotene (BC) is an example of carotenoids and is the major precursor of Vitamin A with immune and antioxidant properties. The role of oxidative stress on hepatic damage caused by acetaminophen (APAP) and the possible protective effects of BC supplement against this damage were investigated. Wistar rats were randomly divided into four groups: control, APAP, BC and APAP+ BC. The control group received distilled water while APAP (750 mg/kg body weight), BC (10 mg/kg/day body weight) were administered to the other groups accordingly. Treatments were administered orally via gavage and lasted for seven consecutive days. Twenty four hours after the last drug administra¬tion, the animals were anaesthetized with diethyl ether and blood was collected from each rat and prepared serum samples were thereafter used for biochemical analy¬sis. The liver from each rat was carefully collected and weighed. They were homogenized with phosphate buffer and used for oxidative analysis. SOD activ¬ity was determined (epinephrine in 0.005 N HCl). CAT (determined by measuring the exponential dis¬appearance of H2O2) and GSH (Ellman’s reagent) activities were determined. Lipid peroxidation was also analyzed by the forma¬tion of malondialdehyde (MDA).The serum levels of SGPT, SGOT, and SAP were determined using an automatic enzyme analyzer (Beckman, California, USA). Values are mean ± SEM, compared with ANOVA to show significant differences among groups, Tukey’s post hoc test was used to determine specific pairs of groups that were statistically different (GraphPad Software, USA).The serum glutamate oxalate transaminase (SGOT) level of the APAP group was significantly increased compared to the control (272.27 ±18.77 vs 197.75 ± 28.20). An increase was also observed in the serum glutamic pyruvate transaminase (SGPT) (82.80±8.91vs 58.40 ±5.76) as well as the serum alkaline phosphatase (SAP) levels of (177.60±19.53 vs 169.80±13.83; p<0.01). These increased levels were ameliorated by the administration of β-carotene. The SOD, GSH and CAT levels of the APAP groups which were significantly decreased (P<0.001) when compared to the control had a boost in the antioxidant level after the application of BC. SOD level was (APAP vs APAP+ BC; 35±1.50 vs 80± 4.05); GSH (APAP vs APAP+ BC; 40±2.75 vs 70± 5.65); CAT levels (APAP vs APAP+ BC; 300±10.50 vs 460± 12.65). The reverse was the case in the MDA activity (APAP vs APAP+ BC; 15±0.5 vs 10± 0.7). The study showed that BC ameliorates the damaging effect of acetaminophen on liver tissues.