Purpose: Low-density lipoprotein receptor-related protein-1 (LRP1) is a large multifunctional peptide which plays a role in diverse cellular processes, including lipid metabolism, cell growth, migration, and regeneration. sLRP1 (soluble form) can be detected in serum and sLRP1 can serve as a biomarker of atherosclerosis and cardiometabolic diseases. This study investigated the concentrations of the circulating serum sLRP1 and explored its potential role as a diagnostic and prognostic biomarker in patients with diabetic retinopathy. Methods: Fifty-two patients with diabetic retinopathy and 71 controls were enrolled based on well-defined eligibility criteria. Venous blood samples were collected after 12 hours of fasting. sLRP1 concentrations were measured using the commercially available ELISA in an accredited laboratory. Results: The mean age of patients and control groups were 63.6 and 48.5 years, respectively. The median disease duration was 8.1 years. The median serum sLRP1 levels were lower in patients with diabetic retinopathy compared to the controls (2.11 µg/mL versus 2.44 µg/mL, p=0.034). No significant correlation was observed between the sLRP1 and serum lipid levels. Conclusions: The sLRP1 levels are low in patients with diabetic retinopathy compared to healthy controls, and future studies are needed to assess sLRP1 as a potential biomarker in diabetic retinopathy.