Endogenous pigment epithelium derived factor (PEDF) shows great potential as a drug target for the treatment of diabetes retinopathy (DR) due to its anti-angiogenesis, anti-inflammatory, neuroprotective and neurotrophic effects. PEDF plays a biological role by combining with receptor proteins on cell membrane surface and regulating a variety of signaling pathways. Low density lipoprotein receptor related protein 6 plays a role in inhibiting oxidative stress reaction, inflammatory reaction, and neovascularization of DR. Adipose triglyceride lipase, laminin receptor, plexin domain containing 1 (PLXDC) 1, PLXDC2 and F1-adenosine triphosphate synthase have the effect of promoting endothelial cell apoptosis, among which PLXDC1 also has neuroprotective effect. By clarifying the receptor that PEDF acts on, exploring the affinity between the receptor and PEDF, the difference in the expression level of each receptor in the process of disease, and the specific function that PEDF plays after binding with specific receptors, we can develop fusion protein drugs for the active domain of high affinity of receptors, have a clearer understanding of the pathogenesis of DR, and take PEDF or PEDF receptor as the target to consolidate the theoretical basis for the development of new therapeutic drugs and strategies for DR.