UNLABELLED: Adenomyosis (ADS) is a common gynecological disorder characterized by dysmenorrhea, menorrhagia, and infertility, which markedly impair women's quality of life. Repeated cyclic bleeding of ectopic endometrial lesions may sustain local inflammation and tissue remodeling, leading to a "menstruation-inflammation-fibrosis" cycle. This study aimed to establish a mouse model that mimics this process and to evaluate the effect of estrogen-progesterone (EP) sequential exposure on uterine fibrosis in adenomyosis. METHODS: A tamoxifen-induced mouse model of adenomyosis was established, followed by EP sequential exposure to induce a menstruation-like process. Histological staining and immunohistochemistry were performed to evaluate lesion formation, inflammatory responses, and fibrosis-related changes in uterine tissues. RESULTS: EP sequential exposure successfully induced menstruation-like changes in the uterus of mice with adenomyosis. Compared with controls, mice exposed to sequential EP showed more prominent endometrial breakdown, inflammatory responses, and fibrotic remodeling. Collagen deposition and the expression of fibrosis-associated markers, including α-SMA, were increased in uterine lesions, indicating aggravated fibrosis. CONCLUSION: EP sequential exposure promotes fibrosis in adenomyosis lesions in mice and may serve as a useful model for investigating the "menstruation-inflammation-fibrosis" cycle in adenomyosis.