Lipoxin A 4 (LXA 4 ) is a lipid mediator that plays an important role in the resolution of inflammation. However, the role of LXA 4 and aspirin (ASA)-triggered lipoxins (ATLs) in inflammatory edema formation remains unclear. Here, we investigated the inhibitory role played by LXA 4 in the carrageenan-induced and other inflammatory mediator-induced edematogenic response in mice, and also assessed the role of ATLs in the anti-edematogenic action of aspirin. Our results showed that LXA 4 (1–20ng/paw or 5μg/kg i.p.) was effective in inhibiting carrageenan-induced paw edema from 30min to 2h. LXA 4 (10ng/paw) was also able to acutely inhibit PAF-, histamine-, PGE 2 - or bradykinin-induced paw edema, as well as the PAF-induced myeloperoxidase activity increase in the paws. Likewise, LXA 4 (10ng/cavity) also inhibited the pleural edema triggered by histamine (1h), and this response was not followed by leukocyte accumulation. Of note, the lipoxin receptor (ALX-r) antagonist Boc2 (butoxycarbonyl-Phe-Leu-Phe-Leu-Phe, 200ng/paw) significantly reverted the anti-edematogenic effect of ASA (300mg/kg p.o.) against carrageenan, PAF, PGE 2 and BK, without affecting the anti-edematogenic action caused by indomethacin (3mg/kg i.p.) in the carrageenan-induced paw edema. Collectively, our results demonstrate for the first time that LXA 4 displays an acute and rapid onset anti-edematogenic activity that does not discriminate among different pro-inflammatory stimuli, an effect that is most likely independent of its action on the leukocyte influx. Finally, the present study demonstrates that ATLs exert a very important role in the acute anti-edematogenic action of ASA.