Pulmonary fibrosis (PF) and pulmonary hypertension (PH) are chronic diseases of the pulmonary parenchyma and circulation, respectively, which may coexist, but underlying mechanisms remain elusive. Mutations in the GCN2 gene (EIF2AK4) were recently associated with pulmonary veno-occlusive disease. This study aims to explore the involvement of the GCN2/eIF2α pathway in the development of PH during PF, in both human disease and in an experimental animal model. Lung tissue from PF patients with or without PH were collected at the time of lung transplantation, and controls were obtained from tumor resection surgery. Experimental lung disease was induced in either male wild-type or EIF2AK4-mutated Sprague-Dawley rats, randomly receiving a single intratracheal instillation of bleomycin or saline. Hemodynamic studies, as well as organ collection were performed 3 weeks post-instillation. Only significant results (p<0.05) are given. In PF lung tissue, GCN2 protein expression was decreased, when compared with controls. GCN2 expression was reduced in CD31+ endothelial cells. In line with human data, GCN2 protein expression was decreased in the lung of bleomycin rats when compared with saline. EIF2AK4-mutated rats treated with bleomycin showed increased parenchymal fibrosis (hydroxyproline levels) and vascular remodeling (media wall thickness) as well as increased right ventricular systolic pressure when compared to wild-type animals. Our data shows that GCN2 is dysregulated in both human and in an animal model of combined PF+PH. The possibility of a causative implication of GCN2 dysregulation in PF and/or PH development should be further studied.