The interleukin-1 family member IL-33 participates in both innate and adaptive immune responses and has been shown to facilitate lung inflammation in T helper-2 (Th2) immune cell models of lung disease. IL-33 acts as an ‘alarmin’ that signals the recruitment of inflammatory cells. IL-6-type (also termed gp130) cytokines can facilitate inflammation and we have shown that pulmonary overexpression of the gp130 cytokine Oncostatin M (OSM) can up-regulate Th2-skewed cytokine levels, eosinophil accumulation, and more recently the expression of IL-33 in C57Bl/6 mouse lungs. However, IL-6 does not in this model. To test whether IL-33 expression is necessary for OSM-mediated inflammatory effects, Adenoviral-OSM(AdOSM) administration was used to transiently overexpress OSM in the lungs of wild-type and IL-33-deficient mice. Mice treated with AdOSM for 7 days showed recruitment of eosinophils and neutrophils to the lung, increased levels of inflammatory chemokines (KC, eotaxin-1, MIP1a, MIP1b), IL-6 and Th2 cytokines (IL-4/IL-5/IL-13), but not IFNgamma or IL-12. The AdOSM-induced production of Th2 cytokines was also associated with an increase in IL-33R+ ILC2 cells (lineage-negative, CD45+, CD90.2+, Sca-1+, T1/ST2+), while overexpression of IL-6 (AdIL-6) did not induce similar effects. OSM-induced neutrophil and eosinophil accumulation was significantly reduced in the lungs of IL-33-deficient mice. This reduction was also associated with a similar decrease or absence in detectable inflammatory and Th2 cytokines. Expression of arginase-1, an OSM-induced protein and marker of M2-like macrophages that develop within a Th2-like environment, was also significantly reduced in IL-33-deficient mice. Taken together, we have identified IL-33 as a critical mediator of OSM-driven Th2-type responses and M2-like arginase-1+ macrophage accumulation in C57Bl/6 mouse lung inflammation. (Supported by Canadian Institutes of Health Research, operating grant # 137013).