Background: To investigate the abnormal expression of circ_0008590 and its parent gene, reticuloendotheliosis viral oncogene related B (RELB) in human retinal microvascular endothelial cells (hRECs) in hyperglycemia and the potential mechanism. Methods: The levels of RELB, circ_0008590, and miR-1243 in hRECs or clinical samples were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Dual-luciferase reporter assay was used to test the interaction between RELB/circ_0008590 and miR-1243. Cell Counting Kit-8 (CCK-8), Transwell, flow cytometry (FCM), wound healing, and tube formation assays were used for the physiological investigation. The interaction between human RELB and circ_0008590 was studied in streptozotocin (STZ) induced diabetic retinopathy (DR) C57BL/6 mice. Results: The levels of circ_0008590 and RELB were increased in hRECs in hyperglycemia; during the progression of DR, the levels of circ_0008590 and RELB messenger RNA (mRNA) in aqueous humor were first decreased and then increased, whereas miR-1243 showed an opposite trend. Both RELB 3'-untranslated region (UTR) and circ_0008590 shared a similar binding site for miR-1243. Further, miR-1243 mimic suppressed the proliferation and migration of hRECs, promoting the apoptosis ratio, which could be rescued by the overexpression of circ_0008590. In STZ-induced DR mice, miR-1243 agomir rescued the effects of the overexpression of human RELB. Conclusions: In hyperglycemia, high expression of RELB/circ_0008590 could be suppressed by miR-1243, and the nuclear factor-κB (NF-κB) pathway is subsequently affected.Keywords: Diabetic retinopathy (DR); circ_0008590; hyperglycemia; miR-1243; reticuloendotheliosis viral oncogene related B (RELB).