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Annona senegalensis Pers. (ANNONACEAE) is a plant which is used in african traditional medicine for the treatment of various diseases. This study aimed to investigate the analgesic and anti-inflammatory activity of total ethereal leaf extract fractions of A. senegalensis. Compounds of methanolic fractions of ethereal leaf extract of A. senegalensis were separated by gel sephadex chromatography, in five fractions (F1, F2, F3, F4, F5). Experiments were performed in acetic acid-induced contortions in mice, carrageenan rat paw edema and phospholipase A2 inhibitory test. The methanolic fraction of total ethereal leaf extract (10 mg/kg, per os) significantly prevented the carrageenan inflammatory edema. The variation of edema is 22.31±3.35 %, 49.66±13.50 %, 52.10±10.02 % respectively at T1h, T3h and T5h. The increased edema after oral administration of F4 fraction administered at 300 µg/kg and 1 mg/kg per os is respectively 52.77±7.36 % and 33.81±6.94 %. The variation of edema in betamethasone group (1 mg/kg, per os) is 23.46±3.99 %. F4 fraction at 300 µg/kg, significantly inhibited 16.39 % of phospholipase A2 enzyme activity. F4 fraction (300 µg/kg, per os) also significantly prevented acetic acid-induced pain in mice. The number of abdominal contortions is 21 versus 72 in control group. F4 fraction compounds have a powerful analgesic and anti-inflammatory activity that involves phospholipase A2 inhibition, comparable to betamethasone profile on pain and inflammation.