IL-25 is a TH2-promoting cytokine, however, its role in regulating the maintenance and function of TH2 memory/effector cells in vivo remains elusive. We have developed a novel mouse model to study the regulation of TH2 memory/effector cells after re-exposure to OVA antigen. Phenotypic analyses reveal that the recalled TH2 memory/effector cells in lung express distinct level of IL-25 receptor (IL-25R), ST2, and OX40. Notably, the frequency of local IL-25R+CD4+ TH2 memory/effector cells in inflamed lung, but not other lymphoid tissues, is elevated after increased numbers of OVA antigen re-exposure. These lung resident IL-25R+CD4+ TH2 memory/effector cells are much more potent to produce TH2 cytokines than the TH2 cells in other lymphoid tissues. Enforced expression of IL-25R by T cells in mice resulted in increased accumulation of local antigen-specific TH2 memory/effector cells, leading to more prominent airway inflammation, compare to those of littermate controls in our novel mouse model of allergic lung diseases. These results suggest that IL-25 may promote allergic inflammation by enhancing the accumulation and function of lung resident IL-25R+CD4+ TH2 memory/effector cells in vivo.