Diabetic retinopathy is one of the microvascular abnormal diseases. In the late stage of disease progression, the antibody of vascular endothelial growth factor can significantly inhibit the formation of new blood vessels and improve macular edema, which is widely used in clinical. However, the aggravation of pro-fibrotic influence after long-term treated by the medicine also attracts a wide range of attention. Connective tissue growth factor, as an important cytokine in intraocular fibrosis, over expressed after treated by the drug, is considered to be one of the most important factors in the side effect of the drug, and is also a potential therapeutic target. After finishing the current research, the regulation mechanism of connective tissue growth factor, includes two ways, regulation of gene expression and direct binding to other cell factors or receptors. Because of its special four module structure, it has many kinds of cell factor specific binding sites, and its regulation mode is more dependent on the latter, which promotes or inhibits the expression of several important cytokine pathways. In diabetic retinopathy, its expression goes throughout the disease process. The accumulation of connective tissue growth factor plays an important role in promoting the thickening of basement membrane and the formation of new blood vessels in the early stage of the clinical stage and the formation of the new blood vessels. In this paper, the regulatory mechanism of connective tissue growth factor and the research progress of this factor in DR are systematically expounded.