Abstract: Objective To investigate the expression and clinical significance of vascular epithelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) and type Ⅳ-collagen(Ⅳ-C) in gestational diabetic placenta. Methods A case-control study was performed in 48 women with gestational diabetes mellitus (GDM) and 36 healthy pregnant women (control), who delivered at Taiyuan Maternal and Infant Health Care Hospital from Jun. 2007 to Dec. 2007. The expressions of VEGF, MMP-9 and Ⅳ-C in placenta were detected by immunohistochemistry. Results The expression of VEGF, MMP-9 and Ⅳ-C in GDM placenta was significantly higher than that of control (70.8% vs 30.6% ,64.6% vs 30.6% ,62.5% vs 27.8%, all P<0.05). For those GDMs whose blood glucose levels were well controlled, the expression of VEGF, MMP-9 and Ⅳ-C (51.9%, 51.9% and 44.4%) showed no difference from the control (P>0.05), however, those GDMs which were poor-controlled, the expression of the three indicators (95.2%, 80.9% and 85.7%) were higher than the control (P<0.05). The expression of MMP-9 was positively correlated with that of VEGF and Ⅳ-C in the GDM group(r=0.579, P<0.01, r=0.596, P<0.01). Conclusions The high expression of VEGF, MMP-9 and Ⅳ-C in GDM placenta may he associated with blood glucose control. Early management of the blood sugar level might alleviate the pathological changes in placenta.