Tissue eosinophilia prevention represents one of the primary targets to new anti-allergic therapies. As lipoxin A 4 (LXA 4) and aspirin-triggered 15-epi-LXA 4 (ATL) are emerging as endogenous “stop signals” produced in distinct pathologies including some eosinophil-related pulmonary disorders, we evaluated the impact of in situ LXA 4/ATL metabolically stable analogues on allergen-induced eosinophilic pleurisy in sensitized rats. LXA 4/ATL analogues dramatically blocked allergic pleural eosinophil influx, while concurrently increasing circulating eosinophilia, inhibiting the earlier edema and neutrophilia associated with allergic reaction. The mechanisms underlying this LXA 4/ATL-driven allergic eosinophilia blockade was independent of mast cell degranulation and involved LXA 4/ATL inhibition of both IL-5 and eotaxin generation, as well as platelet activating factor action. These findings reveal LXA 4/ATL as a novel class of endogenous anti-allergic mediators, capable of preventing local eosinophilia.