Most of the current medical treatments for endometriosis aim to down-regulate estrogen activity. However, a high recurrence rate after medical treatment has been the most significant problem. BAY 11-7085, a soluble inhibitor of nuclear factor-B activation, has been shown to inhibit cell proliferation and induce apoptosis of a variety of cells. To examine the potential application of BAY 11-7085 in the treatment of endometriosis, we investigated the effects of this agent on the cell proliferation and apoptosis of cultured ovarian endometriotic cyst stromal cells (ECSCs) by a modified methylthiazoletetrazolium assay, a 5-bromo-2'-deoxyuridine incorporation assay, and internucleosomal DNA fragmentation assays. The effect of BAY 11-7085 on the cell cycle of ECSCs was also determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSCs using Western blot analysis. BAY 11-7085 significantly inhibited the cell proliferation and DNA synthesis of ECSCs, and induced apoptosis and the G0/G1 phase cell cycle arrest of these cells. Additionally, down-regulation of the B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-X_L expression with simultaneous activation of caspase-3, caspase-8, and caspase-9 was observed in ECSCs after treatment with BAY 11-7085. These results suggest that BAY 11-7085 induces apoptosis of ECSCs by suppressing anti-apoptotic proteins, and that caspase-3-, caspase-8-, and caspase-9-mediated cascades are involved in this mechanism. Therefore, BAY 11-7085 could be used as a therapeutic agent for the treatment of endometriosis.