Endometriosis, characterized by the growth of uterine-like tissue outside the uterus, causes chronic pain and infertility. Current diagnostic and therapeutic strategies have notable limitations, including delayed diagnosis and adverse effects. The transcription factor forkhead box A2 (FOXA2), which is exclusively expressed in the uterine glandular epithelium, regulates key genes involved in endometrial proliferation, differentiation, fertility, and hormone response. While FOXA2 expression is reduced in the endometrial tissue of women with endometriosis, its pathophysiological role in the disease is not well understood. In this study, we report that endometriosis significantly reduced FOXA2 expression in the eutopic endometrium of mice with endometriosis compared to sham controls, accompanied by decreased expression of its downstream gene, CXCL15. To evaluate the effect of FOXA2 loss in endometriosis, we surgically induced endometriosis by transplanting control Rosa26