Objectives: To investigate the expression, DNA methylation status and its regulatory mechanism of tissue factor pathway inhibitor 2 (TFPI-2) in human placenta tissues of preeclampsia (PE). Material and methods: We studied the mRNA and protein expression and the promoter methylation levels of TFPI-2 in the PE placentas compared with those in the normal pregnant (NP) women. Quantitative real-time polymerase chain reaction, immunohistochemistry, western blot, and Sequenom Mass ARRAY were used for placenta tissue detection. Results: The expressions of TFPI-2 mRNA and protein were significantly elevated in the PE placentas when compared with those in the NP ones (P<0.05). Hypomethylation of the TFPI-2 promoter was detected both in PE patients and NP women, with a significant decrease in PE placentas (P = 0.005). The methylation level was significantly decreased at CpG_6 (-168 to -167), CpG_15 (-98 to -97) and CpG_18.19 (-68 to -65) in PE patients than that in normal placentas (P0.05). Conclusion: Over-expression of TFPI-2 and aberrant promoter mythylation status presented in the PE placentas, suggesting that epigenetic mechanism might contribute to the pathogenesis of PE. (C) 2017 Elsevier Ltd. All rights reserved.