Fatty acid-binding protein 4 (FABP4) has been implicated in the pathology of diabetes and macrovascular diseases. Serum FABP4 levels were determined in type 2 diabetic patients without diabetic retinopathy (DR) at admission in order to investigate a possible contribution of FABP4 to the increased risk of 5-year incidence of DR.Cohort study.A total of 738 patients with type 2 diabetes without DR were consecutively enrolled and followed up prospectively. Retinopathy evaluation was annually performed by ophthalmologists in the following 5 years. Multivariate analyses were performed using logistic regression models.During the follow-up period, 152 (20.60% [95% CI: 17.68%-23.51%]) patients developed DR and 60 (8.13% [95% CI: 6.16%-10.10%]) patients developed vision-threatening DR (VTDR). Nonparametric Spearman rank correlation revealed a statistically significant positive correlation between serum FABP 4 level and international Clinical Diabetic Retinopathy Severity Scales (r = 0.348; P < .001). After adjustment for other established risk factors, in multivariate models comparing the third and fourth quartiles against the first quartile of the FABP4, levels of FABP4 were associated with DR and the adjusted risk of DR increased by 124% (OR = 2.24 [95% CI 1.65-3.68], P = .006) and 227% (3.27 [2.04-5.56], P < .001), respectively. Similarly, the adjusted risk of VTDR increased by 140% (OR = 2.40 [95% CI 1.32-3.82], P = .001) and 278% (3.78 [2.17-6.59], P < .001), respectively.FABP4 shows potential as a novel biomarker for DR prediction in Chinese patients with T2DM, and strict glycemic control and more frequent retinal examination should be highlighted for T2DM patients with the highest quartile range of FABP4.Copyright © 2017 Elsevier Inc. All rights reserved.