Pulmonary fibrosis is a severe and progressive lung disease characterized by lung tissue scarring. Transforming growth factor beta 1 (TGFβ1) is crucial in causing pulmonary fibrosis by promoting the activation of fibroblasts and their differentiation into myofibroblasts, which are responsible for excessive extracellular matrix deposition. This study aimed to identify genes activated by TGFβ1 that promote fibrosis and to understand the regulatory pathway controlling myofibroblast. Endothelin-1 (ET-1) was identified as the top-ranking gene in the fibrosis-related gene set using quantitative PCR array analysis. TGFβ1 upregulated EGR1 expression through the ERK1/2 and JNK1/2 MAPK pathways. EGR1 and p-SMAD2 proteins interacted with the ET-1 gene promoter region to regulate TGFβ1-induced ET-1 expression in IMR-90 pulmonary fibroblasts. Mice lacking the Egr1 gene showed reduced ET-1 levels in a model of pulmonary fibrosis induced by intratracheal administration of bleomycin. These findings suggest that targeting EGR1 is a promising approach for treating pulmonary fibrosis, especially idiopathic pulmonary fibrosis, by affecting ET-1 expression and profibrotic reactions.