We designed the present study to elucidate the molecular mechanism for parturition, focusing on p38 mitogen-activated protein kinase (p38). The kinase activity of p38 in mouse uterus was gestation stage-dependent, and was markedly increased on day 19 of gestation and during labor. Immunohistochemical examination with anti-phospho p38 antibody revealed that activated p38 was predominantly localized in decidual stromal cells stained with anti-prolactin antibody. In human primary cultured decidual cells, a p38 inhibitor, SB202190, significantly inhibited both prostaglandin F-2 alpha production and COX-2 expression induced by stimulation with IL-1 beta. These results suggest that the p38 signaling pathway is involved in decidual function at the late stage of gestation and may contribute to parturition.