Background: The periodontal ligament cells (PDL cells) play a key role in the formation of the periodontal ligament but these cells have other functions as well. The PDL cells express estrogen receptors but the functional importance is not known. Estrogen modulates inflammation and our hypothesis is that estrogen protects the periodontium via an anti-inflammatory effect on PDL cells. Aim: To identify genes regulated by estrogen in LPS-treated human PDL cells by whole genome arrays. Materials and methods: PDL cells were obtained from human premolars extracted for orthodontic reasons. The cells were divided into two groups. One group was pre-treated with 17β-estradiol (E2, 100 nM) for 2 h and then with Escherichia coli LPS (500ng/ml) for 24 h. The other group was treated with LPS only. Total RNA was extracted and purified by RNeasy Mini Kit (Qiagen®, USA). A whole genome microarray was performed (Affymetrix®, USA) comparing gene expression in the two groups. The cut-off limit was set to a twofold change. Results and Conclusion: Estrogen caused an up-regulation of 38 genes, while 28 genes were down-regulated. Estrogen regulated genes associated with cell-metabolism and cell-signalling but also genes associated with early the inflammatory response. The functional significance of these findings is now determined by e.g. measuring protein levels with ELISA. We conclude that estrogen regulates gene expression in human PDL cells exposed to LPS.