The development of preeclampsia (PE) seriously affects the health of the mother and the child, but the precise pathogenesis of PE remains elusive. The placenta is considered to play a key role and DNA methylation may be associated with altered placental development and function. The aim of this study was to perform a genome-wide analysis of the DNA methylation profile in placentas from pregnancies with severe preeclampsia. The authors analyzed normal and placental tissues with PE for aberrant DNA methylation using methylated DNA immunoprecipitation (MeDIP) and a human CpG island plus promoter microarray. The methylation status of identified candidate genes were validated by bisulfite sequencing PCR (BSP). Microarray analysis identified 296 genes that showed significantly aberrant DNA methylation in preeclampsia (PE). These genes were located more frequently in chromosome 1 (10.5%, P=0.005), chromosome 12 (8.1%, P=0.062) and chromosome 19 (7.4%, P=0.117). Functional analysis divided these genes into different functional networks. In addition, the methylation profile of six of these genes (CAPN2, EPHX2, ADORA2B, SOX7, CXCL1 and CDX1) in nine patients with PE was validated by BSP. This study demonstrated aberrant patterns of DNA methylation in PE, which may be involved in the pathophysiology of PE. Future work will assess the potential prognostic and therapeutic value for these findings in PE.