The processes of implantation and placentation involve various cell events, such as degradation and remodeling of extracellular matrix, cellular proliferation, apoptosis, and differentiation. Evidence indicates that members of the matrix metalloproteinase (MMP) family play crucial roles in these processes. In the present study, the expression and localization of MMP-26/endometase/matrilysin-2 in human cytotrophoblast cells as well as its regulation by activin A were investigated by using methods of reverse transcriptase-polymerase chain reaction, immunohischemistry and fluorescence immunohistochemistry. The results showed that MMP-26 was strongly localized in villous trophoblast cells, and weakly in some of the villous mesenchyma. The mRNA level of MMP-26 in chorionic villi was high in early pregnancy, and was down-regulated from gestational week 10 on, reaching a very low level at week 26. However, its mRNA expression was significantly up-regulated in the term placenta. In the primary cultured cytotrophoblast cells, the mRNA expression of MMP-26 maintained a stable level during gestational week 6~12. Moreover, the expression of MMP-26 in the cytotrophoblast cells was stimulated by activin A in a dose-dependent manner. All the data indicated that MMP-26 may be involved in trophoblast invasion during early pregnancy and placenta detachment at the time of delivery. There may exist autocrine/paracrine regulation of MMP-26 expression in cytotrophoblast cells.