Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme which converts the essential amino acid tryptophan to kynurenine. The aim of this study was to investigate the expression and regulation of Ido1 in mouse uterus during decidualization. The results showed that Ido1 mRNA expression gradually increased from day 1 to 4 of pregnancy and reached the peak level on day 4. On days 5-8 of pregnancy, a low level of Ido1 expression was observed in the uteri. Simultaneously, Ido1 mRNA was also lowly expressed in the decidualized uterus and the stromal cells treated with 8-Br-cAMP. Under in vitro decidualization, the expression of Ido1 mRNA gradually declined. Further studies found that overexpression of Ido1 can inhibit the expression of decidualization marker genes PRL, IGFBP1 and Dtprp under in vitro decidualization while inhibition of Ido1 with L-1-MT can induce the expression of these marker genes. Ido1 can prevent uterine stromal cells proliferation and enhance the expression of the Bax gene and increase the Bax/Bcl2 ratio under in vitro decidualization. Additionally, Ido1 can also modulate the expression of the MMP2 gene. In the uterine stromal cells, estrogen and progesterone can stimulate the expression of Ido1. These data indicate that Ido1 may play an important role during mouse decidualization and may be regulated by estrogen and progesterone in the uterine stromal cells.