Objective:To investigate the differential expression profile of circular RNA (circRNA) in high glucose-cultured human retinal vascular endothelial cells (HRVECs).Methods:HRVECs were divided into high glucose group, normal control group and hypertonic control group, and were cultured in 25 mmol/L glucose medium, 5.5 mmol/L glucose medium and 19.5 mmol/L mannitol+ 5.5 mmol/L glucose medium for 24 hours accordingly.The differentially expressed circRNA molecules between high glucose group and normal control group were screened by circRNA microarray analysis.The expression of the most significant differentially expressed circRNAs in different groups was verified by real-time quantitative PCR.The possible microRNA (miRNA) targets were analyzed through the Circular RNA Interactome database.Results:It was found that 448 circRNAs were differentially expressed (FC≥1.5 or FC≤0.67, P<0.05) in high glucose-cultured HRVECs, among which 182 were up-regulated and 266 were down-regulated.The top 3 significantly up-regulated circRNAs were hsa_circ_0002938, hsa_circ_0008036, and hsa_circ_0001946, and the top 3 significantly down-regulated circRNAs were hsa_circ_0035277, hsa_circ_0008344, and hsa_circ_0001874.Compared with normal control group and hypertonic control group, the relative expressions of top 3 up-regulated circRNAs were significantly enhanced and the relative expressions of top 3 down-regulated circRNAs were significantly reduced in high glucose group, showing statistically significant differences (all at P<0.05).No significant difference was found in the differentially expressed circRNAs between normal control group and hypertonic control group (all at P>0.05). Conclusions:CircRNAs are differentially expressed in high glucose-cultured HRVECs, and the differentially expressed circRNAs may be involved in the regulatory mechanism of diabetic retinopathy.