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This cross-sectional study included 142 type 2 diabetes patients, with and without diabetic retinopathy. Compared with healthy controls, serum FGF21 levels were elevated in subjects with type 2 diabetes but without retinopathy (mean [SD] 103.50 [75.75] pg/ml versus 99.00 [126.75] pg/mL), and even higher across different stages of diabetic retinopathy (233.00 [109.00] pg/ml for nonproliferative diabetic retinopathy and 215.00 [122.00] pg/ml for proliferative diabetic retinopathy). After adjustment for potential confounders, FGF21 was shown to be the only significant factor associated with diabetic retinopathy in type 2 diabetes patients.