OBJECTIVE This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Patients with T2DM (n = 191) underwent an oral glucose tolerance test, a liver 1H-MRS, and a liver biopsy when indicated. PRO-C3, PRO-C5, and PRO-C6 were blindly assessed. RESULTS PRO-C3 performed well for the diagnosis of moderate-to-advanced (area under the receiver operating characteristic curve [AUROC] 0.81 [95% CI 0.74–0.88]) and advanced (AUROC 0.88 [0.80–0.95]) fibrosis in T2DM patients. Its performance was similar to that of AST to platelet ratio index (APRI) (AUROC 0.83 and 0.87, respectively) and Fibrosis-4 (FIB-4) (AUROCs 0.83 and 0.86, respectively) scores. Use of PRO-C5 and PRO-C6 did not improve the accuracy to detect liver fibrosis. After 18 months, PRO-C3 changes were associated with changes in fibrosis stages. CONCLUSIONS PRO-C3 performed well for the detection of fibrosis in T2DM patients and showed promising results for prediction of histological changes in fibrosis stage with treatment.