This study was conducted to determine the antimutagenic potential of aqueous extract of Cassia occidentalis against the chromosomal aberrations (CA) produced in vivo by benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) in mice. Animals (male mice) were treated with three doses of plant extract (50 mg/kg, 250 mg/kg and 500 mg/kg) for 7 days prior to the administration of single dose of mutagens (B[a]P 125 mg/kg oral; CP 40 mg/kg i.p.). The results indicated that C. occidentalis was not genotoxic per se and exerted no other toxic signs and symptoms in treated animals. The chromosomal aberrations produced by B[a]P and CP were significantly reduced (p < 0.001) by C. occidentalis pre-treatment. Furthermore, animals treated with plant extract showed a reduced level of cytochrome P 450 (Cyt P 450) and elevated levels of glutathione S-transferase (GST) activity and glutathione content in the liver. It seems that C. occidentalis exerts its antimutagenic activity by modulating the xenobiotic activation and detoxification mechanisms.