Objective To investigate the expression of hypoxia-inducible factor-1α(HIF-1α),matrix metalloprotein-ase(MMP)-1 and MMP-2 in the serum of patients with diabetic retinopathy(DR),and to analyze their relationship with the stage of DR and angiogenesis.Methods A total of 280 patients with type 2 diabetes mellitus(T2DM)and no DR who were hospitalized in our hospital from December 2020 to December 2021 were selected as the T2DM group;276 DR patients who were hospitalized in the ophthalmology department of our hospital during the same period were selected as the DR group;another 282 healthy subjects who underwent physical examination in our hospital were selected as the normal group.There were no significant differences in gender and age distribution among the normal group,T2DM group and DR group(both P＞0.05).According to the results of fundus examination and fluorescein angiography,the patients in the DR group were divided into non-proliferative diabetic retinopathy(NPDR)group(129 patients)and proliferative diabetic reti-nopathy(PDR)group(147 patients).The fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c)and serum HIF-1 α,MMP-1,MMP-2 levels of subjects in the normal group,T2DM group and DR group,as well as NPDR group and PDR group were compared.The serum basic fibroblast growth factor(bFGF),angiopoietin-1(Ang-1)and vascular endo-thelial growth factor(VEGF)levels of subjects in the normal group,T2DM group and DR group,as well as NPDR group and PDR group were compared.Pearson correlation analysis was used to analyze the correlation between serum HIF-1α,MMP-1,MMP-2 and bFGF,Ang-1,VEGF levels in DR patients.Results The FPG,HbA1c and serum HIF-1α,MMP-1,MMP-2 levels of the T2DM group and DR group were higher than those of the normal group,and the differences were statis-tically significant(all P＜0.05).The serum HIF-1α,MMP-1 and MMP-2 levels of the DR group were significantly higher than those of the T2DM group(all P＜0.05);there were no significant differences in FPG and HbA1 c between the two groups(both P＞0.05).The serum HIF-1α,MMP-1 and MMP-2 levels of the PDR group were significantly higher than those of the NPDR group(all P＜0.05);there were no significant differences in FPG and HbA1c between the two groups(both P＞0.05).The serum bFGF,Ang-1 and VEGF levels of the T2DM group and DR group were higher than those of the normal group,and the differences were statistically significant(all P＜0.05).The serum bFGF,Ang-1 and VEGF levels of the DR group were significantly higher than those of the T2DM group(all P＜0.05).The serum bFGF,Ang-1 and VEGF levels of the PDR group were significantly higher than those of the NPDR group(all P＜0.05).Pearson correlation analysis showed that HIF-1α,MMP-1 and MMP-2 were positively correlated with bFGF,Ang-1 and VEGF levels in DR patients(all P＜0.05).Conclusion The serum HIF-1α,MMP-1 and MMP-2 levels of DR patients are abnormally elevated,and are closely related to the progression of DR and angiogenesis.These parameters can be used to predict the disease development trend and guide clinical intervention.