Background and Purpose: Heart failure (HF) affects 64 million people worldwide. Despite advancements in prevention and therapy, quality of life remains poor for many HF patients due to target organ damage. Pulmonary manifestations of HF are well-established. However, difficulties in the treatment of HF patients with chronic lung phenotypes remain, as standard therapies are often complicated by contraindications. Here, we verify the downregulation of the cystic fibrosis transmembrane regulator (CFTR) in the HF lung, a concept that may provide new mechanism-based therapies for HF patients with pulmonary complications. Experimental Approach: Ligation of the left anterior descending coronary artery in mice was used to induce myocardial infarction (MI). At 10 weeks post-MI, pharmacological CFTR corrector therapy (Lumacaftor (Lum)) was applied systemically or lung-specific for 2 weeks, and the lungs were analysed using histology, flow cytometry, Western blotting, and qPCR. Key Results: Experimental HF associated with an apparent lung phenotype characterized by reduction of pulmonary CFTR+ cells, vascular remodelling, and pronounced tissue inflammation as evidenced by infiltration of pro-inflammatory monocytes and elevation of classically-activated macrophages in the lung. PharmacologicalCFTR correction with Lum mitigated the HF-induced downregulation of pulmonary CFTR expression, increased the proportion of CFTR+ cells in the lung, and diminished the HF-associated elevation of classically-activated non-alveolar macrophages within the lungs with implication for vessel wall thickness. Conclusion and Implications: Collectively, our data suggest that pharmacological CFTR correction possesses the capacity to alleviate HF-induced inflammation in the lung and may emerge as treatment option for HF patients with chronic lung phenotypes.