Experiments were conducted with the aim of evaluating the ameliorative effect of methanolic extract of Phyllanthus niruri (MEPN) on chlorpyrifos (CPF)-evoked erythrocyte fragility and lipoperoxidative changes in Wistar rats. Thirty five rats divided into 5 groups of 7 animals in each group served as subjects for this study. Rats in group I were given only soya oil (2 ml/kg) while those in group II were administered with CPF only (10.6 mg/kg ~1/8th LD50 determined in a previous study). Rats in group III were given MEPN only (500 mg/kg). Rats in group IV were pretreated with MEPN (250 mg/kg) and then dosed with CPF (10.6 mg/kg), 30 minutes later. Rats in group V were pretreated with MEPN (500 mg/kg) and then CPF (10.6 mg/kg), 30 minutes later. The different regimens were orally administered once daily for a period of 28 days. At the end of the study, the rats were sacrificed and blood samples collected were evaluated for osmotic fragility, while the erythrocyte packets prepared from another batch of blood samples were examined for malonaldehyde (MDA) concentration. The results showed that rats exposed to CPF only demonstrated a significant increase in erythrocyte fragility and MDA concentration compared to the other groups. This study indicated that MEPN protected rats from CPF-induced increased erythrocyte fragility and lipoperoxidative changes, probably as a result of its flavonoid contents, which has been shown to have antioxidant activity.