Hbegff/f;Lyz2Cre+ mice are protected from bleomycin-induced fibrosis despite similar levels of acute lung injury. Hbegff/f;Lyz2Cre+ mice have lower levels of hydroxyproline (A), decreased expression of profibrotic genes (B) Collagen 1, Collagen 3, and Fibronectin, improved lung histology (C), and improved pulmonary function as noted by the Hbegff/f;Lyz2Cre+ mice expanding to higher lung volumes at lower pressures than Lyz2Cre+ control mice measured by P-V loops 21 days post-bleomycin treatment (D). Additionally, levels of total protein (E) and albumin detected in the BAL fluid (BALF) (F) is not different between Lyz2Cre+ and Hbegff/f;Lyz2Cre+ mice three days post-bleomycin treatment, suggesting initial lung injury between genotypes is the same. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. Lines in (C) are 100 μm length. All data are combined from 2–4 experiments or are representative of 2–4 experiments, n = 4–6. n.s. = not significant; P–V = pressure–volume.