Objective To examine the protective effect of pancreatic kininogenase on retinopathy in diabetes mellitus rats, and explore its mechanism of action. Methods Sixty specific-pathogen-free rats were randomly divided into a blank group, model group, and treatment group, with 20 rats in each group. The model group and treatment group were given a single intraperitoneal injection of 60 mg / kg streptozotocin to establish a rat diabetes model. Rats in the blank group were intraperitoneally injected with an equivalent amount of 0. 1 moL/ L sodium citrate. Rats in the treatment group were treated by intraperitoneal injection of 0. 8 U of pancreatic kininogenase, while the blank group and model group were intraperitoneally injected with 0. 2 mL of normal saline once a day for 2 weeks. Hematoxylin and eosin staining was used to observe pathological changes of retinal ganglion cells ( RGCs). Apoptosis of RGCs was detected by TUNEL staining. Activity of superoxide dismutase ( SOD) and malondialdehyde ( MDA) content in the retina were detected by enzyme- linked immunosorbent assay. mRNA and protein expression of Notch1 and HES-1 were detected by quantitative RT-PCR and western blotting. Results In the blank group, the structure of each layer of retinal tissue was clear, RGC nuclei were clear and orderly, and apoptotic cells were only occasionally seen. Compared with the blank group, RGCs in the model group were arranged disorderly, the nuclei were sparse, the number of RGCs was significantly reduced, apoptosis rate was increased, SOD activity of retinal tissue was decreased, and MDA content was increased (P< 0. 05). Compared with the model group, the structure of each layer of retinal tissue in the treatment group was clear, the nuclei of RGCs were clear and regular, the number of RGC layer cells was increased, apoptosis rate was decreased, SOD activity of retinal tissue was increased, and content of MDA was decreased (P< 0. 05). The quantitative RT-PCR and western blotting result showed that mRNA and protein expression levels of Notch1 and Hes1 were decreased in the model group compared with the blank group (P< 0. 05). Compared with the model group, mRNA and protein expression levels of Notch1 and Hes1 in the treatment group were increased ( P< 0. 05). Conclusions Pancreatic kininogenase can protect and improve diabetic retinopathy. The mechanism may be related to the activation of the Notch1 / HES-1 signaling pathway.