Abstract: The effect of single dose chloroquine treatment on enzymatic antioxidant profiles and lipid peroxidation in the blood of rabbits was investigated. Treatment of rabbits with 10 mg kg-1 (single dose) chloroquine resulted in increases of 53.6, 11.6 and 3.6% (p<0.05) in the activity of superoxide dismutase at 6, 12 and 24 h, respectively after drug administration while the activity of catalase was significantly reduced by 37.1, 15.5 and 2.9% (p<0.05) at the same intervals when compared with control. Malondialdehyde level increased (p<0.05) by 11.9 and 1.9% at 6 and 12 h, respectively, but decreased by 13.8% at 24 h relative to control. Reduced glutathione was decreased by 41.9, 38.7 and 3.2% at the same hourly intervals when compared with control (p<0.05). The findings in this study suggest that chloroquine treatment altered enzymatic antioxidant defense systems and elevated lipid peroxidation in the blood of rabbits with the most noticeable alteration observed 6 h after drug administration perhaps due to the peak plasma concentration of chloroquine which is usually reached between 3 and 5 h after drug administration. Oxidative stress is thus induced in the blood by chloroquine at least within 6 h of its administration.