Objective:To investigate the subcellular localization of decidual protein induced by progesterone(DEPP) as well as its effect on cell viability and gene expression in human umbilical endothelial cell line EA.hy926. Methods:Recombinant adenovirus expressing human DEPP was generated. The subcellular localization of DEPP was investigated by using immunofluorescence and Western blot assay with cells infected by ADV-DEPP. Cell viability was determined by using MTT assay. Apoptotic or necrotic cell numbers were measured by flow cytometry. Angiogenesis related protein expression pattern in response to DEPP over-expression was examined by using antibody microarray. Results:Over-expressed DEPP was localized both in the nucleus and cytoplasm in EA.hy926 cell. Compared with control cells,DEPP expression led to more severe cell shrinkage and detachment after adenovirus infection. MTT assay showed that cell viability was significantly decreased with exogenous DEPP. Flow cytometry analysis revealed that the main cell death induced by DEPP was necrosis. Finally,angiogenesis antibody microarray indicated that DEPP induced the increase of 7 genes and the reduction of 70 genes expression in endothelial cells. Conclusion:With increased expression,DEPP led to endothelial cell damage and may be involved in the regulation of angiogenesis.