Azadirachta indica A. Juss., Meliaceae, or Indian neem is a plant used to treat inflammatory disorders. Total polysaccharide (TPL) and FI (fractioned by ion exchange chromatography) from the seed tegument of A. indica were evaluated in models of acute inflammation (paw edema/peritonitis) using Wistar rats. Paw edema (measured by hydroplethysmometry) was induced s.c. by λ-carrageenan (300 μg), histamine (100 μg), serotonin (20 μg), compound 48/80 (10 μg), prostaglandin (PGE 2 30 μg) or L-arginine (15 μg). Peritonitis (analyzed for leukocyte counts/protein dosage) was induced i.p. by carrageenan (500 mg) or N-formyl-methionyl-leucyl-phenylalanine (fMLP 50 ng). Animals were treated i.v. with TPL (1 mg/kg) or FI (0.01, 0.1, 1 mg/kg) 30 min before stimuli. FI toxicity (at 0.1 mg/kg, i.v. for seven days) was analyzed by the variation of body/organ mass and hematological/biochemical parameters. TPL extraction yielded 1.3%; FI, presenting high carbohydrate and low protein content, at 0.1 mg/kg inhibited paw edema induced by carrageenan (77%), serotonin (54%), PGE 2 (69%) and nitric oxide (73%), and the peritonitis elicited by carrageenan (48%) or fMLP (67%), being well tolerated by animals. FI exhibited potent anti-inflammatory activity, revealing to be important active component in traditionally prepared remedies to treat inflammatory states.