Objective：To investigate the effect of inhibition of proinflammatory cytokines produced by macrophages on the progesterone resistance in endometriosis. Methods：The primary ectopic endometrial stromal cells（ESCs）of 15 endometriosis women were cultured. The chemotactic test was used to detect the role of CXCL12 expressed by ectopic ESCs in the recruitment of macrophages. LPS（100 ng/mL）was used to stimulate macrophages to express pro-inflammatory cytokines after macrophages were transfected with nuclear factor（NF）-κB decoy oligonucleotides（ODNs）. The electrophoretic mobility shift assay（EMSA）assay was used to detect the activation of NF-κB in macrophages after LPS stimulation，and ELISA was used to detect the expression of interleukin-1β（IL-1β）and tumor necrosis factor-α（TNF-α）in macrophages. In the co-culture system of ectopic ESCs and macrophages，the effect of NF-κB decoy ODNs on the decidualization of ectopic ESCs was observed. Results：CXCL12 secreted by ectopic ESCs played a role in the recruitment of macrophages in endometriosis. NF-κB decoy ODNs significantly inhibited the expression of pro-inflammatory cytokines in macrophages. In co-culture system of macrophages and ectopic ESCs，NF-κB decoy ODNs enhanced the progesterone-induced decidualization of ectopic ESCs by inhibiting the production of pro-inflammatory cytokines from macrophages. Conclusion：This study indicates that NF-κB targeting therapy of macrophages maybe an opportunity for mitigating the inflammatory response and progesterone resistance in endometriosis.