Aims: Distemonanthus benthamianus is a widespread plant in West Africa. The bark of its stem is used popularly to treat a variety of illnesses, including fever, bronchitis, rheumatism and malaria. The objective of this work is to evaluate the antipyretic activity of the aqueous extract of the bark of Distemonanthus benthamianus. Materials and Methods: The aqueous extract of the bark of D. benthamianus was tested for their acute oral toxicity in rats. Antipyretic activity was studied in rats of the Wistar strain made feverish after subcutaneous injection of an aqueous suspension of brewer's yeast (Saccharomycete cerevisiae) 20% compared to aspirin. Results: This study showed that administration of the extract at doses of 300, 2000 and 5000 mg / kg / kg dry extract in rats showed no acute toxicity or adverse effects. The results showed that the best antipyretic activity of the extract was recorded at a dose of 800 mg / kg, at the third hour, with a decrease in fever from 39.29 ± 0.14°C to 37.75 ± 0.25°C, i.e. a percentage inhibition of 57% against 62% for the standard molecule (p> 0.05). At this dose, CRP was 3.85 ± 0.1 mg / L compared to that of the healthy control which was 2.78 ± 0.35 mg / L. The results of the albumin assay did not show a significant difference between the treated and untreated fever groups and the healthy control group. In addition, the results showed that the leukocyte level in the feverish control rats is very high (18.84 103 / mm3 of leukocytes) compared to the healthy and treated control rats. Conclusion: The aqueous extract of the bark of Distemonanthus benthamianus is not oral toxic and has interesting antipyretic activities similar to aspirin. The results obtained confirm the validity of the traditional indication of this plant in the management of fever by African populations.