Endometriosis is known as extra uterine presence of endometrial glands and stromas, and is associated with pelvic pain and infertility. It causes serious physical, mental, and social implications and is also an economic burden to the society. However, the pathogenesis is not fully understood. Several theories have been proposed to explain the histogenesis of endometriosis, including implantation, inflammmation, or genetic factors. Recently, the role of L-selectin in leukocyte extravasation and the role of macrophages in endometriosis have been extensively studied. Although yielding promising results, previous studies have yet to determine the association between L-selectin and macrophages in human endometriosis. This monograph reports a breakthrough study that concluded L-selectin gene P213S polymorphism is associated with endometriosis and that M2 Macrophage has a significant role in developing endometriosis. On confirming the role it has on the events of endometriosis, together with additional studies, L-selectin gene is expected to be a marker in diagnosing this disease.