To evaluate the association between elevated levels of plasma pentraxin 3 (PTX3) and the development and/or progression of diabetic retinopathy (DR). In this case-control study, 92 diabetic patients with DR (group 3), 30 diabetic patients without DR (group 2), and 41 normal subjects (group 1) were enrolled. Log-transformed values of plasma PTX3 and high-sensitivity C-reactive protein (hsCRP) concentrations were measured and used in our analysis. For subgroup analysis, group 3 was divided into four subgroups: mild, moderate, severe nonproliferative, and proliferative DR. In our 163 participants, average plasma PTX3 levels were 916.1 ± 532.2, 1093.7 ± 1034.2, and 1817.9 ± 1776.9 pg/mL for groups 1, 2, and 3, respectively. The duration of diabetic mellitus (DM), glycated hemoglobin (HbA1c), log hsCRP, and log PTX3 were significantly different between the three groups (P = 0.008, P < 0.001, P = 0.046, and P < 0.001, respectively). In subgroup analysis, plasma log PTX3 levels increased in correlation with the severity of DR (R = 0.372, P < 0.001). Multivariate logistic analysis showed that the correlation between DR development and duration of DM and log PTX3 values was significant (P = 0.014 and P = 0.025, respectively), whereas correlation with log hsCRP values was not significant in univariate analysis (P = 0.129). The receiver operating characteristic curves of DR development were plotted using log PTX3 and log hsCRP values, and the area under the curves was found to be 0.721 (P = 0.001) and 0.614 (P = 0.087), respectively. Plasma PTX3 is positively associated with DR development and progression, and may be a more accurate predictor of DR development than hsCRP.