Aims: To investigate in vitro antioxidant/radical scavenging activities and hepatoprotective ability of ethanolic leaf extracts of Cassia occidentalis (COLEX) in male Wistar rats treated with sodium arsenite (NaAsO2). Study Design/Methodologies: Using four different methodologies, the anti-oxidant/free radical scavenging activities of COLEX were determined in comparison with standard antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). For the hepatoprotection study, four groups of rats were used. Groups A: Control group given distilled water only; B: Given NaAsO2 at 2.5 mg•kg-1 bw/day (p.o.) for 2 weeks; C: Administered COLEX alone at 200 mg•kg-1 bw a day for 2 weeks (p.o.); D: Pre-treated with COLEX for 2 weeks followed by NaAsO2. The activities of the enzymes aspartate and alanine aminotransferases (AST and ALT), alkaline phosphatase (ALP) and γ- glutamyl transferase (γGT) were determined in the treated and control animals as indices of hepatotoxicity. Place and Duration of the Study: The animal treatment and analyses were carried out at Department of Biochemistry, University of Ibadan between February and June 2008. Results: At 25, 40 and 50 μg•ml-1 concentrations of the extracts or the antioxidants, the reducing power is of the order BHA > BHT > COLEX. At 50 μg•ml-1, the percentage inhibitions of peroxidation by COLEX, BHA and BHT were respectively 96.2%, 97.3% and 98.4% while percentage DPPH scavenging effect of COLEX, BHA and BHT were 62.5%, 67.5% and 61.3% respectively. The H2O2 scavenging activities were respectively 53.0%, 85.3% and 97.8% for COLEX, BHA and BHT. Pre-treatment with COLEX before administration of NaAsO2 led to significant (p < 0.05) reduction in the mean liver and serum γGT, and serum ALP and AST activities when compared with group administered only NaAsO2. Conclusion: COLEX exhibited hepatoprotective effects against NaAsO2 toxicity in male rats.