Introduction: Afzelia africana is a large tree that is widespread in West Africa. Its bark is used in traditional medicine to treat rheumatism, edema, and pain. In our previous researches, we studied the phytochemical characteristics of the aqueous extract of trunk bark, which showed a high content of phenolic compounds and particularly flavonoids, which are known to have anti-inflammatory properties. This extract has been formulated as a topical hydrogel, and preclinical animal studies on the chronic and acute inflammation model have demonstrated anti-inflammatory activity comparable to that of diclofenac with an inhibition rate of 85.31%. With the aim of industrial production of improved traditional medicine, while preserving biodiversity, we investigated whether the leaves of A. africana could advantageously replace the trunk back. The objectives were to first study the phytochemically composition of the aqueous and hydroethanolic extracts of the leaves in comparison to that of the trunk bark, and then to evaluate its anti-inflammatory activity in an animal model. Methodology: The main families of secondary metabolites were investigated in the aqueous and hydroethanolic extracts. The polyphenol and flavonoid contents were determined by spectrophotometric assay, and the results were expressed as gallic acid equivalents and quercetin equivalents, respectively. Anti- inflammatory activity was determined using an acute ear inflammation model induced by topical application of xylene in mice. Mice were divided into four groups. In the negative control group, mice were not treated; betamethasone was used as a positive control; aqueous and hydroethanolic extracts were administered at a dose of 20 mg per ear. Doses were administered topically to mice. The contralateral ear served as a control. All animals were sacrificed 0.5, 1, and 4 hours after xylene, and then two ears were cut along the pinna. The pinna was harvested and weighed. The inhibition rate was calculated in the different groups. Structural changes in the inner ear wall after xylene application were evaluated by histology on sections of the animals' ears. Results: The results showed that, the aqueous leaf extract of A. Africana has a similar secondary metabolite composition to the trunk bark extract, containing tannins, alkaloids, flavonoids, steroids, coumarins, and quinones. The aqueous and hydroethanolic leaf extracts contained similar levels of total polyphenols, with 196.44 ± 4.22 and 214.58 ± 1.78 mg/g in gallic acid equivalents, respectively. The hydroethanolic leaf extract contained significantly higher levels of flavonoids than the aqueous leaf extract, with 59.16 ± 0.22 mg/g in quercetin equivalents compared to 32.23 ± 4.22 mg/g. In addition, the flavonoid content of the aqueous leaf extract was comparable to that of the trunk bark, with 25.8 mg/g ± 0.26. Treatment with the aqueous and hydroethanolic extracts of A. Africana leaves significantly inhibited ear edema 0.5, 1, and 4 hours after xylene application, with inhibition percentages of 44.49% and 12.39% after 0.5 hour, 80.26% and 80.67% after 1 hour, and 63.97% and 49.44% after 4 hours respectively. These inhibition percentages were comparable to those of animals treated with betamethasone, which had inhibition percentages of 56.38%, 75.30%, and 76.39% after 0.5, 1, and 4 hours, respectively. Conclusion: The trunk bark of A. Africana is used in traditional medicine to treat inflammatory diseases and pain. Its topical application inspired us to study the phytochemical composition and anti-inflammatory activity of the trunk bark. Although it demonstrated an interesting anti-inflammatory potential, in order to protect this precious resource, we investigated the potential of the leaves. The phytochemical study showed that, as for the trunk bark, the leaves have a high content of active metabolites, particularly polyphenols, which are known for their anti-inflammatory potential. The anti-inflammatory activity of the leaf extracts has been demonstrated, making the leaves a good candidate for the development of improved traditional medicines.