Fibroblasts are pleomorphic cells that have a multi-directional effect on organ morphogenesis, tissue homeostasis, and immune response. In fibrotic diseases, fibroblasts synthesize large amounts of extracellular matrix (ECM), leading to scarring and organ failure. Purine-rich box1 (PU.1) is a specific transcription factor of hematopoietic cell and belongs to the E26 transformation specificity (ETS) family. Recently, it was found that the transcription factor PU.1 is an important regulatory factor of the profibrotic gene expression program. TGF-β had been proved to play an important role in many ocular tissue fibrosis diseases, and up-regulated the expression of PU.1 in fibroblasts producing ECM in a Smad-3 dependent manner. We explore the effect of PU.1 on fibrosis of different ocular tissues from this perspective. This article reviews the role of PU.1 and its effects on fibrosis of ocular tissue and other tissues.