Diabetic retinopathy (DR) is a severe complication of diabetes mellitus (DM), and it is challenging to diagnose DR at an early stage by conventional methods. The aim of the present work is to propose an innovative approach to monitor the process of DR from scratch. The plasma metabolites changed with DM were obtained by time-dependent metabolomics and lipidomics; the change of retinal function was measured by b-wave amplitude and total Ops-wave amplitude in electroretinography (ERG). Multivariate statistical analysis, logistic regression and correlation analysis were employed to identify metabolic markers from metabolites for the monitoring of DR and investigate the relationship between metabolic markers and retinal function. The metabolic markers LPE18:0, LPC15:0, SM d14:2/26:0, SM d12:0/28:2 and MG 21:0 associated with DR can be utilized as metabolic markers to monitor the process of DR; The decrease in myo-inositol and LPC22:5 and increase in xylonic acid and TAG10:0/16:0/18:1 indicated retinal dysfunction. The levels of metabolic markers can be used as an indicator of the onset of DR or as a means of monitoring changes in retinal function.