Fagara zanthoxyloides is a medicinal plant used in traditional medicine for the treatment of elephantiasis, toothache, sexual impotence, malaria, dysmenorrheal and abdominal pain among rural dwellers. The aim of the present study was to evaluate the in vivo and in vitro anti-inflammatory effect of the methanol extracts of the leaves of Fagara zanthoxyloides to validate its use in folklore medicine. The analysis of the phytochemical content of the leaf extract of Fagara zanthoxliodes revealed the presence of different secondary metabolites (tannins, saponin, terpenoids, steroids, flavonoids, alkaloids, phenols and glycoside) in varying proportions. In the systemic oedema of the rat paw, scalar doses (50, 100 and 250 mg/kg b.w) of the extract significantly (p < 0.05) suppressed the development of paw oedema induced by egg albumin at different time intervals (0.5 hr- 5 hrs). This compares well with a standard anti–inflammatory drug indomethacin (10 mg/kg b.w). Varying doses of the extract (1.0, 1.2, 1.4, 1.6 and 1.8 ml) significantly (p< 0.05) inhibited phospholipase A₂ activity in a concentration-related manner provoking inhibition comparable to that of prednisolone, a standard anti-inflammatory drug. Similarly, the extract significantly (p< 0.05) inhibited CaCl₂-Induced platelet aggregation in a dose and time dependent manner. The extract also significantly (p< 0.05) inhibited hypotonicity induced membrane stabilization. These results indicate that the extract produced potential anti-inflammatory activity which could be as a result of the rich phytochemical constituents.