Background and aims: Sesamum radiatum leaves are commonly used by African and Ivorian people in particular to treat various diseases. However, few studies have been done on the pharmacological properties and even less on the acute toxicity of this medicinal plant in Côte d'Ivoire. Also, the present work was carried out in order to contribute to correcting this through a comparative study of the acute oral and intraperitoneal toxicity of the aqueous extract of the leaves (ESera) in the female Wistar rat. Méthodes: According to the modified OECD 423 method, 2 groups of 6 rats were treated with ESera at 50 mg/kg and 2000 mg/kg in a single dose respectively by intraperitoneal and oral administration in comparison with the control group (NaCl 0.9 %). Dice weighing at regular intervals of 2 days of body weight and the removal of some organs and blood samples at the end of the 14-day observation period allowed the measurement of biological parameters. Results: Irrespective of the administration route, ESera did not cause clinical signs of suffering, behavior change and death in rats. The morphology and the relative weight of the organs (heart, kidneys, liver and lungs) were not modified. Treated animals exhibited weight growth kinetics similar to those of the controls. Greater weight gains (p < 0.05) were obtained with ESera. The study carried out on the blood samples showed statistically significant changes (p < 0.05) in certain hematological and serum biochemical parameters. The changes observed were greater with ESera 50 mg/kg intraperitoneal administration. Conclusion: Sesamum radiatum aqueous extract did not cause death or organ changes in rats during the 14 days of observation.However, in order to better determine its toxicity, other studies must be carried out due to the disturbances observed in hematological parameters, transaminases and electrolytes. Keywords: Acute toxicity, Hematological parameters, Biochemical parameters, Organ biometry