The effect of activity directed fractions of vernonia amygdalina on the levels of urea, uric acid; total and conjugated bilirubin in wistar albino rats during acetaminophen induced hepatotoxicity was investigated in this research. The forty-eight (48) wistar albino rats used were divided into 8 groups of six rats each. Group one, the normal control group received distilled water, group two received only paracetamol throughout the experimental period. Groups three to eight were administered with 171.43mg/kg body weight of paracetamol and treated with 200mg/kg body weight of activity directed fractions of vernonia amygdalina throughout the 14 days of treatment. Result shows significantly lower levels (p<0.05) of uric acid in the paracetamol, chloroform, ethyl acetate, butanol, methanol and residue E treated fractions compared to the normal control. However, the benzene fraction had a higher uric acid level (p<0.05) compared to the normal control. Urea levels significantly increased (p<0.05) in groups treated with fractions of chloroform and residue E while it significantly decreased (p<0.05) in the butanol treated group over the normal control group. Total bilirubin levels were significantly higher (p<0.05) in the treatment groups compared to the normal control. Whereas, the conjugated bilirubin level was non - significantly higher (p>0.05) than the normal control, the levels were significantly higher (p<0.05) in groups treated with fractions of benzene and butanol compared with the normal control levels, levels of conjugated bilirubin were non significantly higher (p>0.05) in chloroform and residue E treated groups when compared with the normal control. Non - significantly higher levels (p>0.05) of conjugated bilirubin were observed in all treated groups except the ethyl acetate fraction group compared to the paracetamol group. Vernonia amygdalina fractions have the ability to protect against acetaminophen induced liver damage coupled with antioxidative potentials. This suggests that vernonia amygdalina is suitable for the treatment of acetaminophen induced hepatotoxicity.