Objective: To study the serum ecto-5'-nucleotidase (CD73) and apelin levels in patients with diabetic retinopathy (DR) and the clinical significance. Methods: A total of 108 patients with type 2 diabetes treated in our hospital between April 2013 and February 2016 were collected and divided into non-diabetic retinopathy (NDR) group (n=51), background diabetic retinopathy (BDR) group (n=40) and proliferative diabetic retinopathy (PDR) group (n=17) based on the results of fundus fluorescence angiography. Enzyme-linked immunosorbent assay (ELISA) was used to determine CD73 and apelin level immediately after admission; thiobarbituric acid method and xanthine oxidase method were used to determine the serum levels of oxidative stress indicators; ELISA method was used to determine the levels of angiogenesis indexes and inflammatory factors; Pearson test was used to analyze the correlation of serum CD73 and apelin levels with the illness-related indexes in patients with DR. Results: Serum CD73 and apelin levels of BDR group and PDR group were significantly higher than those of NDR group, and serum CD73 and apelin levels of PDR group were significantly higher than those of BDR group; serum malondialdehyde (MDA), advanced oxidation protein products (AOPP), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-毩 (TNF- 毩), hypersensitive C-reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), angiogenin-2 (Ang-2) and hypoxia-inducible factor 1毩 (HIF-1毩) levels of BDR group and PDR group were significantly higher than those of NDR group while total antioxidant capacity (TAOC), superoxide dismutase (SOD) and interleukin-10 (IL-10) levels were lower than those of NDR group, and the changes in above indexes of PDR group were more significant; Pearson test showed that serum CD73 and apelin levels in patients with DR were directly correlated with the levels of illness-related indexes. Conclusion: CD73 and apelin expression are abnormally high in patients with DR, and their expression is directly correlated with the disease severity, and can be used as the reliable indicators for early diagnosis and prognosis judgment of DR.