Inducible BALT (iBALT) is associated with immune responses to respiratory infections as well as with local pathology derived from chronic inflammatory lung diseases. In this study, we assessed the role of oncostatin M (OSM) in B cell activation and iBALT formation in mouse lungs. We found that C57BL/6 mice responded to an endotracheally administered adenovirus vector expressing mouse OSM, with marked iBALT formation, increased cytokine (IL-4, IL-5, IL-6, IL-10, TNF-A, and IL-12), and chemokine (CXCL13, CCL20, CCL21, eotaxin-2, KC, and MCP-1) production as well as inflammatory cell accumulation in the airways. B cells, T cells, and dendritic cells were also recruited to the lung, where many displayed an activated phenotype. Mice treated with control adenovirus vector (Addl70) were not affected. Interestingly, IL-6 was required for inflammatory responses in the airways and for the expression of most cytokines and chemokines. However, iBALT formation and lymphocyte recruitment to the lung tissue occurred independently of IL-6 and STAT6 as assessed in gene-deficient mice. Collectively, these results support the ability of OSM to induce B cell activation and iBALT formation independently of IL-6 and highlight a role for IL-6 downstream of OSM in the induction of pulmonary inflammation. © 2013 by The American Association of Immunologists, Inc.