Objective: To evaluate the antimalarial activity of the aqueous extract of Euphorbia(E.) cordifolia Elliot against Plasmodium(P.)berghei-infected mice.Methods: Thirty healthy Swiss mice were intraperitoneally inoculated with 200 μL of P. berghei parasitized-erythrocytes and divided into five groups, and then daily treated for 5 d with single dose of 10 mL/kg of distilled water for malaria control, 10 mg/kg of chloroquine for the chloroquine control and 100, 200 and 400 mg/kg of the aqueous extract of E. cordifolia for the three test groups. Parasitaemia was monitored by Giemsa-staining. At the end of the treatment, animals were sacrificed, and blood was collected for haematological and biochemical analyses. Organs were collected for biochemical and histopathological analyses. Statistical significance(P<0.05) was evaluated by analysis of variance followed by the Tukey post-test using Graphpad prism 7.0. Results: E. cordifolia extract decreased the parasite load to 2.46%, with an effective dose(ED_(50)) of 113.07 mg/kg compared to the malaria group where the parasite load increased to(46.46±10.28)%. E. cordifolia extract prevented hypoglycaemia, anaemia, leucocytosis and thrombocytopenia, attenuated the increase of transaminases activities, bilirubin and creatinine rate, and improved catalase and superoxide dismutase activities, while reducing malondialdehyde contents in the liver and kidney. E. cordifolia extract significantly prevented histological damages observed in the malaria control group. No acute toxicity sign was observed in mice with plant extract at the dose up to 5 000 mg/kg.Conclusions: E. cordifolia extract at 200 and 400 mg/kg showed significant antimalarial effects. This results support its traditional use in the treatment of malaria.