The cyclin dependent kinase inhibitor P21 CDKN1A has been shown to be upregulated during differentiation and after DNA damage in somatic cells. We examined the expression of P21 CDKN1A and of γ-H2AX during the differentiation of germ cells in normal mouse testis. P21 CDKN1A was normally expressed in in a variable mode in different cell types (spermatogonia, spermatocytes, spermatids, Sertoli cell) located since the basal till the lumen of the seminiferous tubules. Moreover, in agreement with γ-H2AX expression, P21 maybe involved in different cell cycle checkpoints in spermatocytes such as a pre-replication, XY body inactivation, a mid-pachytene and a metaphase I checkpoints. Finally, in comparison to control, the p21 deficient mouse testis show elevated numbers of apoptosis of elongated spermatids within stages VIII-IX but any difference in the number of spermatogonia mitosis.These results suggest that P21 also may take part in the regulation of the differentiation of the male germ cells and may have a role in spermatogonia not related with a mitotic checkpoint.