Purpose: In this work, we investigated the protective action of Coutarea hexandra aqueous stem bark extract (Ch-E), associated with a commercial antivenom or as a stand-alone therapy, on the acute systemic envenomation induced by Lachesis muta muta in rats.Methods: Male Wistar rats (300-350 g) were exposed to L. m. muta venom (1.5 mg/kg -i.m.) and then treated with a polyvalent antivenom (antivenom:venom ratio 1:3 'v/w' -i.p.), Ch-E (100 mg/kg -i.p.) or combining both of these agents. After 120 min envenomation, animals were anesthetized in order to collect blood samples through intracardiac puncture and, subsequently, euthanized for collecting tissue samples; the hematological-biochemical and histopathological analyses were performed through conventional methods.Results: Venom caused pronounced local oedema, necrosis formation and subcutaneous haemorrhage; Ch-E alone or combined with antivenom prevented the occurrence of subcutaneous haemorrhage. Ch-E administered alone or associated with antivenom effectively prevented the increase of serum creatine kinase (CK) and alanine aminotransferase (ALT) release; Ch-E reduced the release of the serum biomarker (CK-MB) for cardiotoxicity only in association with antivenom. Venom caused pronounced inflammatory responses associated with neutrophilia, eosinophilia and monocytosis; Ch-E alone also contributed significantly to reduce the venom-induced leukocytosis mainly due to its suppressive action on neutrophils. Ch-E prevented the venom-induced increase of reticulocytes either alone or in the presence of antivenom; however, no group had erythrocyte alterations.Ch-E produced effective protection against venom-induced hepatic and renal morphological alterations similarly to antivenom action. Conclusion:Ch-E shows to be an important source of biomolecules with therapeutic potential to prevent efficiently a number of systemic disorders caused by L. m. muta venom in rats, e.g., myotoxicity, hepatotoxicity, inflammatory responses.