The research was set to assess the antioxidant effect of Vernonia amygdalina aqueous extract on lead acetate poisoned Wistar rats. Blood lead determination and assessment of antioxidant status was carried out on five groups of rats, each group consisting of eight rats. Group I were unchallenged and unsupplemented while groups II-V were poisoned with a 150ppm lead acetate in water for 14 days. Thereafter, group II remained unsupplemented with V.Amygdalina extract, while groups III, IV and V were supplemented with 25, 50 and 75mg/kg body weight of extract for 10days. A statistically significant difference was observed when the SOD and CAT activities in groups II and III were compared to that of the control group. Similarly, significant variations were observed when the serum TBARS and blood lead levels in groups II, III and IV were compared with that of control. These values reveal a fairly proportional increase in antioxidant but reduced blood lead levels in response to increasing dosage of extract. Thus, V. amygdalina aqueous extract was able to restore the antioxidant parameters and blood lead levels back to normal. It appears to possess a dose dependent antioxidant and toxic lead excreting property. These activities may be due to the presence of phytochemical antioxidant and lead removing factor(s)/principle(s) which, if properly harnessed, can be used in the treatment of oxidant challenges and lead contamination.