Effects of ROS generation have been postulated to be major contributors to lead-exposure related disease. The aim of the study was to investigate the effect of aqueous extract of wormwood (Artemisia absinthium) on oxidative stress in rats protractedly exposed to lead. Aqueous extract of wormwood plant was administered orally (200 mg.kg−1 body weight). Plasma vitamin C, E and non-protein thiol concentrations, red blood cells (RBC) thiobarbituric acid reactive substances, reduced glutathione levels and haemolysis test were evaluated. In addition, RBC antioxidant enzymes activities such as superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase were also estimated. After 11-weeks, significant decreases of plasma vitamin C, E, non protein-thiol (NP-SH) and RBC-reduced glutathione levels were observed in Pb compared to control group (−32.9%, −57.1%, −53.1%, −33.9%, respectively); superoxide dismutase, glutathione peroxidase, uric aminolevulinic acid and haemolysis test significantly increased in Pb compared to control group (+64.3%, +40.3%, +145%, +44.3%, respectively). In our investigation, after 4-weeks of treatment all treated groups did not show any difference compared to the control group, except for glutathione peroxidase and RBC-superoxide dismutase activity (−15.7% and +16.4%, respectively). The findings of this study suggest that wormwood (Artemisia absinthium) extract restored the enzymes activities perturbed by exposure to lead, and had a protective role against lipid peroxidatio