OBJECTIVE: To evaluate placental cyclophilin A (CyPA) expression and assess its association with maternal/fetal health outcomes in pregnant women with gestational diabetes mellitus (GDM). STUDY DESIGN: A total of 43 pregnant women (23 GDM and 20 non-GDM) underwent a 50-g glucose challenge test (GCT) at 24-28 weeks' gestation. A GCT cutoff of < 140 mg/dL was selected. Women with an elevated GCT underwent prompt diagnostic testing via a 3-hour glucose tolerance test. Immunohistochemistry for CyPA was performed on formalin-fixed and paraffin embedded sections. Finally, the relationship between placenta CyPA reactivity and the clinical findings of GDM was evaluated. RESULTS: The expression of placental CyPA was significantly different between pregnant women with GDM and non-GDM subjects. There was an increased expression of CyPA in trophoblasts, capillary endothelium, and decidua of GDM pregnancies as compared with those of non-GDM subjects (p=0.0007, 0.0012, and 0.0019, respectively). CyPA expression in the capillary endothelium was correlated with the presence of maternal/fetal complications and placental changes associated with GDM. Additionally, CyPA expression in the trophoblasts was strongly correlated with placental changes. CONCLUSION: The discovered differences indicate a possible relationship between GDM and the immunohistochemical expression of CyPA in placental tissue. © Science Printers and Publishers, Inc.