Background <p>Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients. However, effective treatments for non-proliferative DR (NPDR) are limited, especially in the early stage. Remote ischemic conditioning (RIC) has shown great promise in protecting retinal tissues from ischemic damage, but its therapeutic potential in NPDR remains unclear. This study aims to evaluate the safety and efficacy of RIC in patients with mild to moderate NPDR and to provide preliminary data for the design of future multicenter clinical trials.</p> Methods <p>A single-center, randomized, controlled trial was conducted to assess the impact of RIC on patients with mild to moderate NPDR. Participants were randomly assigned to either the RIC group or the sham group. The primary outcome is the change in DR Severity Score from baseline to 1 year after RIC treatment. Secondary outcomes included incidence of PDR, changes in retinal vascular parameters, inflammatory markers, and visual function. Safety assessments included adverse events and any RIC-related complications.</p> Discussions <p>This study aims to conduct a pilot clinical randomized controlled trial to evaluate the safety and efficacy of RIC in treating NPDR. The findings are intended to provide preliminary data on the potential of RIC as an early intervention for NPDR, which may inform the design of future larger-scale clinical studies.</p> Trial registration <p>Clinicaltrials.gov, identifier: NCT06713720, Registration Date: 2024.11.21.</p>