Objective To investigate the expression of tumor suppressor gene p16~(INK4A) in mouse endometrium during the estrus cycle and early pregnancy and its possible role in blastocyst implantation. Methods Reverse transcription polymerase chain reaction(RT-PCR) was used to detect the expression of p16~(INK4A) mRNA,immunohistochemistry and Western blotting were applied to detect p16~(INK4A) protein in mouse endometrium tissues during the estrus cycle and early pregnancy. Results The intensity of p16~(INK4A) mRNA expression in mouse early pregnancy was higher than that in the estrus cycle.Compared with the other 3 stages, the level of p16~(INK4A) mRNA expression at estrus was obviously higher. During the early pregnancy, the level of p16~(INK4A) mRNA expression increased steadily from day 2 to day 5,reaching the maximal level on day 5,then decreasing. Both immunohistochemical and Western blotting analysis showed the same results in expression patterns of p16~(INK4A) protein for mouse endometrium tissues as those results of RT-PCR.Conclusion p16~(INK4A) is involved in the embryos penetrating into the endometrial barrier.