OBJECTIVE To assess the relationship between serum insulin-like growth factor I (IGF-I) and diabetic retinopathy. METHODS This was a clinic-based cross-sectional study conducted at the Emory Eye Center. A total of 225 subjects were classified into four groups, based on diabetes status and retinopathy findings: no diabetes mellitus (no DM; n=99), diabetes with no background diabetic retinopathy (no BDR; n=42), nonproliferative diabetic retinopathy (NPDR; n=41), and proliferative diabetic retinopathy (PDR; n=43). Key exclusion criteria included type 1 diabetes and disorders that affect serum IGF-I levels, such as acromegaly. Subjects underwent dilated fundoscopic examination and were tested for hemoglobin A1c, serum creatinine, and serum IGF-I, between December 2009 and March 2010. Serum IGF-I levels were measured using an immunoassay that was calibrated against an international standard. RESULTS Between the groups, there were no statistical differences with regards to age, race, or sex. Overall, diabetic subjects had similar serum IGF-I concentrations compared to nondiabetic subjects (117.6 µg/l versus 122.0 µg/l; p=0.497). There was no significant difference between serum IGF-I levels among the study groups (no DM=122.0 µg/l, no BDR=115.4 µg/l, NPDR=118.3 µg/l, PDR=119.1 µg/l; p=0.897). Among the diabetic groups, the mean IGF-I concentration was similar between insulin-dependent and non-insulin-dependent subjects (116.8 µg/l versus 118.2 µg/l; p=0.876). The univariate analysis of the IGF-I levels demonstrated statistical significance in regard to age (p=0.002, r=-0.20), body mass index (p=0.008, r=-0.18), and race (p=0.040). CONCLUSIONS There was no association between serum IGF-I concentrations and diabetic retinopathy in this large cross-sectional study.