Purpose:　The　etiology　of　idiopathic　orbital　inflammatory　pseudotumors　(IOIP)　is　unknown.　Epstein-Barr　virus　(EBV)　infection,　which　causes　significant　lymphocyte　infiltration,　has　been　proposed　to　be　involved　in　IOIP.　This　study　tries　to　validate　the　relationship　between　EBV　infection　and　the　development　of　IOIP.　Methods:　Eleven　surgical　samples　from　IOIP　patients　and　four　non-IOIP　control　samples　from　surgery　removal　of　eye　due　to　trauma　were　analyzed　by　microarray.　The　data　were　confirmed　by　real　time　RT-PCR.　The　existence　of　EBV-DNA　segments　in　IOIP　samples　was　determined　by　PCR.　Results:　Hierarchical　clustering　of　microarray　data　successfully　distinguished　the　IOIP　group　and　the　non-IOIP　control　group.　The　gene　EBI2,　usually　induced　by　EBV　infection,　was　significantly　up-regulated　in　the　IOIP　group　(max　=　11.7-fold　over　control).　EBV-DNA　was　detected　in　9/10　(90%)　of　the　IOIP　samples　and　in　0/4　of　the　control　samples.　Up-regulation　of　EB12,　the　immunoglobulin　kappa　light　chain　(IGKC)　and　the　immunoglobulin　heavy　chain　gene　1(IGHA1)　were　detected　in　the　IOIP　group　compared　to　the　control　group.　Conclusion:　Collectively,　these　findings　suggest　that　IOIP　may　be　related　to　EBV　infection　and　IGKC　and　IGHA1　activation.　Furthermore,　we　hypothesize　that　the　expression　of　the　EBI2　gene　may　serve　as　a　molecular　marker　for　IOIP.　More　IOIP　patient　samples　and　detection　of　EBV　related　genes　(EBER1,　EBNA2　and　LMP1)　expression　need　to　be　investigated.　©2010　IEEE.