Objective To investigate the relationship between Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and endometriosis. Methods TWEAK mRNA and protein concentrations in paired samples of eutopic endometrial tissue from women with and without endometriosis, and also of ectopic endometrial tissue from women with endometriosis were measured by Real-time PCR, immunohistochemistry and Western blotting, respectively. Results Compared with control endometrium from women without endometriosis and eutopic endometrium from women with endometriosis, TWEAK expressions were reduced on the ectopic endometrium (P Conclusion TWEAK is expressed on the endometrium of reproductive women, and its concentration rises in secretory phase, compared with that in proliferative phase. Patients with endometriosis had a lower expression of TWEAK on ectopic endometrium, which may lead to a decreased level of apoptosis on endometrial cells. Consequently, endometrial cells were able to survive outside uterus helping the development of endometriosis.