Objective: To identify differentially expressed proteins from the serum of women with and without adenomyosis and to explore the potential pathogenesis of adenomyosis. Design: Serum samples from patients with adenomyosis were compared with samples from healthy controls. Setting: University hospital. Patient(s): Twenty patients with adenomyosis and 20 healthy volunteers. Intervention(s): Collection of serum samples. Main Outcome Measure(s): Protein expression of serum was evaluated with iTRAQ (isobaric tags for relative and absolute quantitation) technology, and the validation of protein was performed with Western blot. Result(s): A total of 167 proteins were identified from 1,406 distinct peptides using iTRAQ technology. Twenty-five proteins were abnormally expressed in adenomyosis patients compared with the control group; 4 of these proteins were significantly down-regulated and 21 were significantly up-regulated in women with adenomyosis. Western blotting was used to validate the relative increases in serum protein levels for three of the identified proteins. Conclusion(s): The differentially expressed proteins identified in our study are mainly involved in cell adhesion, the immune response, and the inflammatory response. On the basis of the results of this study, it can be concluded that these mechanisms may play an important role in the pathogenesis of adenomyosis. Additionally, these proteins may provide clues for not only a promising biomarker for the diagnosis of adenomyosis but also a potential target for therapeutic intervention. (C) 2013 by American Society for Reproductive Medicine.