In this study we have examined the role of phosphoinositide 3 kinase (PI3K), a class Ib PI3K, in contributing to airway remodeling utilizing PI3K deficient mice exposed to chronic allergen challenge. WT mice sensitized to OVA and chronically challenged with OVA for one month developed significantly increased levels of eosinophilic inflammation and airway remodeling. In contrast, PI3K deficient mice challenged with OVA had significantly reduced numbers of BAL and peribronchial eosinophils compared to WT mice. There was no significant difference in the number of bone marrow or circulating peripheral blood eosinophils in comparing WT mice and PI3K deficient mice suggesting that trafficking of eosinophils into the lung was reduced in PI3K deficient mice. PI3K deficient and WT mice had similar levels of IL-5 and eotaxin-1. The reduced eosinophil recruitment to the airway in PI3K deficient mice challenged with OVA was associated with significantly reduced numbers of TGF1+ peribronchial cells, reduced numbers of pSmad 2/3+ airway epithelial cells and pSmad 2/3+ peribronchial cells, as well as significantly reduced levels of peribronchial fibrosis (quantitated by trichrome staining and image analysis, as well as by lung collagen levels). In addition the area of peribronchial -smooth muscle staining was significantly reduced in PI3K deficient compared to WT mice. Overall, this study demonstrates an important role for PI3K in mediating allergen induced eosinophilic airway inflammation, and airway remodeling suggesting that PI3K may be a novel therapeutic target in asthma.