Decidualization is critical to pregnancy in primates and rodents. Endometrial stromal cells undergo the mesenchymal-epithelial transition to transform into decidual stromal cells to provide nutrition and support vascularization during decidualization. Laminins, as the main component of the epithelial basement membrane, regulate cellular adhesion, growth, migration, and differentiation. Our previous study showed that laminin α5β2γ1 strongly expressed in mouse decidua. However, the regulation and function of laminin α5β2γ1 during endometrium decidualization are still unknown. Here, our study reveals robust expression of laminin α5β2γ1 in mice and artificially induced mice deciduoma. And laminin α5β2γ1 is also upregulated during mice and human in vitro decidualization. We demonstrate that progesterone regulates the expression of laminin α5β2γ1 during in vitro decidualization in mice. Interestingly, coated-laminin α5β2γ1 promotes the mesenchymal-epithelial transition in mouse and human uterine stromal cells.