Purpose: The present study was undertaken to examine the expression level of p16 mRNA in mouse hematopoietic stem cell after irradiation and to explore its molecular mechanism.Methods and Materials:Bone marrow mononuclear cells was isolation from 30 C57 male mice and then lineage negative hematopoietic (Lin -) cells was sorted using magnetic bead.The hematopoietic stem cell was divided into 5 groups, including control group, radiation group, p38 inhibition group (SB203580 (5 umol) was added into culture medium 30 minutes before radiation) and transcription inhibition group.Except the control group, the other four groups were exposed to γ ray at a dose of 4 Gy.The expression status of p16 mRNA was examined using Real-time PCR after 5 days.For the transcription inhibition group, actinomycin D (5ug/ml) was added into culture medium 3 hours before RNA extraction.Results: Comparing with the control group, the expression of p16 in radiation group was significant increased, showing radiation can induce the expression of p16 in hematopoietic stem cell.In contrast, the p16 expression level in SB203580 group was not increased after radiation.These data suggested that the increased p16 expression in hematopoietic stem cell after irradiation was mediated by p38 signal pathway.Comparing with control group, the p16 expression level in transcription inhibition group was still increased, suggesting the stability of p16 mRNA was increased.Conclusion: These data showed that the increased expression of p16 in mouse hematopoietic stem cell was mediated by p38 signal pathway.Moreover, this kind of increasing was partly due to the increased stability of p16 mRNA.