Depletion of NK cells by anti-asialo GM1 antibody is a commonly used approach to study the contribution of NK cells to a wide range of immune-related pathophysiological processes. However, this is the first study to our knowledge that has investigated the use of anti-asialo GM1 in depleting NK cells during BIPF. Here we show that treatment of mice with anti-asialo GM1 antibody during BIPF results in significant systemic and airway NK cell abrogation but ultimately does not alter lung fibrosis. Before performing the in vivo NK cell depletion experiments, we sought to fully evaluate the kinetic profile of NK cell migration into the airways during BIPF. Consistent with another report, the acute inflammatory phase of BIPF was characterized by a large infiltration of neutrophils. As the disease evolved towards fibrosis, there was an increase in airway-infiltrating macrophages, T cells and B cells, with T cells and macrophages being the predominant cell types on day 21. Interestingly, NK cells were present in the airways over the entire course of disease, although they represented a minor TC-F 2 fraction of the total leukocyte population on any given day. NK cells migrated into the airways on day 1 after bleomycin injection; their numbers peaked on day 10, and a significant number of NK cells were also present on day 21. The role of natural killer cells in blocking fibrotic disease is well documented in the liver, and recent publications provide some evidence that they might have similar anti-fibrotic functions in the lungs. NK cells are thought to protect against fibrosis through two different mechanisms: 1) by releasing anti-fibrotic IFN-c or, 2) by directly killing collagen producing fibroblasts. In fibrotic lungs, NK cells are reported to be active participants in an early stage IFN-c burst, which is a characteristic of the inflammatory phase TC-E 5008 post-bleomycin injection10, 19, 20. Similar to their functional capabilities in liver fibrosis, NK cells may also dampen fibrosis during the fibrotic phase, by killing activated fibroblasts. Thus, the antifibrotic effects associated with NK cells have the capacity to impact the different pathophysiological phases of BIPF. NKT cells were reported to protect against fibrosis by releasing IFN-c. Furthermore, mice treated with anti-NK1.1 antibody, which depletes both NKT cells and NK cells, resulted in worse fibrosis in the BIPF model. Anti-asialo GM1 selectively depletes NK cells and basophils but spares NKT cells, and according to the literature basophils are not involved in BIPF or clinical pulmonary fibrosis.