Maspin is a member of the serine protease inhibitor family with tumor suppressing activity in breast cancer. Maspin expression was found in normal breast epithelial cells, but was frequently decreased in breast cancer cells and lost in metastatic cells. In this study, we examined the regulatory mechanism of maspin expression and described the re-activation of maspin expression in a series of maspin-negative breast cancer cell lines. All of the 6 maspin-negative breast cancer cells showed induction of maspin promoter activity in a promoter reporter assay. In addition, the treatment of 5-aza-2(') deoxycytidine, trichostatin A or a combination of both led to the re-expression of maspin in a series of maspin-negative breast cancer cell lines. These findings indicate that DNA methylation and/or histone deacetylation are/is partially responsible for the silencing of maspin gene expression in breast cancer cells. The re-expression of maspin by pharmacological intervention potentially offers a promising new target as a therapeutic option in breast cancer.