Objective: This study aimed to explore the effect of COX-2 selective inhibitor (celecoxib) on adenomyosis and its mechanism. Methods: By establishing a mouse model of adenomyosis and using celecoxib to treat adenomyosis, newly born female mice were randomly divided into a control group, adenomyosis model group, and celecoxib group. Hematoxylin-eosin (H&E) staining was used to observe the depth of endometrial infiltration of mouse adenomyosis. RT-PCR (reverse transcription PCR) and western blot were used to detect the expression of Cyclooxygenase-2 (COX-2), Vascular growth factor (VEGF), Nerve growth factor (NGF), and Corticotropin-releasing hormone (CRH) mRNA and protein in mice before and after celecoxib treatment. Results: After treatment with celecoxib, the depth of endometrial infiltration of mouse adenomyosis was reduced. COX-2 and VEGF decreased significantly after celecoxib inhibited expression of COX-2 (P0.05). Conclusion: This study indicated that COX-2 may be an important factor related to the pathogenesis of adenomyosis, and it may become an important molecular target for the treatment of adenomyosis.