Objective To observe the serum vascular endothelial growth factor (VEGF),apelin and heme oxygenase-1 (HO-1) levels in patients with type 2 diabetes mellitus (T2DM) and to explore their their relationship with diabetic retinopathy (DR).Methods A total of 208 patients with T2DM and 50 healthy subjects (control group) from the Central Hospital of Western Hainan during January 2014 and December 2017 were selected in this study.Vision,slit lamp microscope,indirect ophthalmoscope and FFA examinations were performed on all the subjects.According to the results of the examinations combined with the DR clinical staging criteria,the patients were divided into non-DR (NDR) group,non-proliferative DR (NPDR) group,and proliferative DR (PDR) group,with 72,76 and 60 patients in each,respectively.The clinical data of each group were recorded,and the levels of fasting blood glucose (FPG),HbA1c,total cholesterol (TC),three acylglycerol (TG),high density lipoprotein (HDL-C),low density lipoprotein (LDL-C),VEGF,apelin and HO-1 were detected in each group.The receiver operating characteristic curve (ROC) were used to analyze the value of VEGF,apelin and HO-1 in predicting the occurrence of PDR.Correlation analysis of serum VEGF,Apelin and HO-1 with clinical parameters in PDR patients by Pearson correlation analysis.Results The level of VEGF (56.82± 10.16 vs 91.74±22.83,140.15±36.40,195.28±42.26 pg/ml)and apelin (2.95±0.53 vs 4.68±0.74,7.25±1.13,10.16± 1.35 ng/ml) in PDR group were significantly higher than those in NPDR,NDR and control groups (F=17.306,21.814;P＜0.05).The level of HO-1 (50.37±10.14 vs 43.58±8.16,30.25t6.28,22.60±4.72 mmol/L) in PDR group was significantly lower than those in NPDR,NDR and control groups (F=15.827,P＜0.05).The ROC curve analysis showed that the best cut-offvalues of serum VEGF,apelin and HO-1 were 162.50 pg/ml,8.30 ng/ml,27.13 mmol/L,and the three combined to predict PDR of AUC (95％CI)was 0.906 (0.849-0.962),and their sensitivity (90.3％) and specificity (83％) were better.The correlation analysis showed that the VEGF,apelin and HO-1 of PDR patients were correlated with the course of diabetes (r=0.382,0.416,-0.36;P＜0.05),FPG (r=0.438,0.460,-0.397;P＜0.05) and HbAlc (r=0.375,0.478,-0.405;P＜0.05),and the serum VEGF were correlated with apelin and HO-1 (r=0.793,-0.594;P＜0.01).Conclusion Elevated serum VEGF and apelin levels and reduced HO-1 levels are associated with the progression of DR,and the three combination helps predict the occurrence of PDR.