Background <p>Long non-coding RNAs (lncRNAs) emerge as crucial regulators in diabetic retinopathy (DR).</p> Objectives <p>This study examined the expression profile of lncRNA SNHG17 in DR patients, and the underlying mechanism was probed in human retinal microvascular endothelial cells (hRMECs).</p> Materials and methods <p>120 healthy controls (HC), 100 patients with T2DM, and 253 patients with DR were enrolled. hRMECs were treated with high glucose (HG) to mimic DR in vitro. qRT-PCR was performed for mRNA measurement. Cell viability and migration were detected under diverse conditions. Claudin-5 (CLDN5) concentration was detected via ELISA. The predicted targeting relationship was verified via luciferase reporter assay.</p> Results <p>SNHG17 was notably downregulated in patients’ serum and linked to DR progression. Among these patients, serum SNHG17 was the lowest in those with proliferative DR (PDR). In vitro, SNHG17 overexpression significantly boosted proliferation, migration and CLDN5 expression of HG-exposed hRMECs while inhibiting their apoptosis. SNHG17 functioned as a sponge for miR-34a-5p, whose upregulation reversed SNHG17’s effects on hRMECs. CDK6, a target of miR-34a-5p, was downregulated in HG-treated hRMECs, and its serum levels correlated negatively with miR-34a-5p across all participants.</p> Conclusion <p>Downregulation of SNHG17 was linked to the onset and development of DR. Overexpression of SNHG17 can recover the proliferation and migration of hRMECs that were suppressed by HG through sponging miR-34a-5p, and CDK6 may be the target of the SNHG17/miR-34a-5p axis.</p> Clinical trial number <p>Not applicable.</p>