Objective: To explore whether and how angiotensin II (AngII) induced lung fibroblast (LF) activation by regulating Fcor/FOXO1 axis via GLUT1-mediated mitochondrial oxidative stress and metabolic reprogramming. Methods: In vitro, primary LF mRNA was collected after AngII stimulation for RNA-seq. Then, glucose metabolism, mitochondrial oxidative stress, and LF activation markers collagen I and ?-SMA were examined. In vivo, mice PF models were established by bleomycin (BLM). Results: RNA-seq results indicated that Fcor was highly expressed in LF treated with AngII, which was verified in vitro and in vivo. Foxo1 mRNA was no change, but protein level was upregulated as ac-FOXO1. Collagen I and ?-SMA expressions were decreased after knockdown Fcor or inhibit FOXO1. RNA-seq results also suggested that KEGG pathway was enriched to glucose metabolism and ROS after AngII treatment. In vitro, mitochondrial SOD2/NOX4 was imbalanced, and thus mitochondrial ROS (mtROS) was upregulated by AngII. Fcor/FOXO1 axis promoted GLUT1-mediated glucose uptake, resulting in mitochondrial oxidative stress. Furthermore, mtROS induced metabolic reprogramming: OCR decreased, ECAR increased, and extracellular lactate upregulated. GLUT1 inhibitor BAY876 reduced mitochondrial oxidative stress, metabolic reprogramming, and LF activation. In vivo, FOXO1 and ac-FOXO1 colocalized with ?-SMA in fibrotic lung tissue; BAY876 and mtROS scavenger Mitoq reduced BLM-induced PF, respectively. Conclusion: AngII induced LF activation by regulating GLUT1-mediated mitochondrial oxidative stress and metabolic reprogramming which were regulated by Fcor/FOXO1 axis.