Endometriosis is a gynaecological disorder characterised by the presence of endometrial cells from the lining of the uterus outside the uterine cavity, commonly presenting as lesions on the peritoneal wall or surface of the ovary, and affects 10% of reproductive-aged women. From an immunological standpoint, lesion development in endometriosis can be broadly classified into two stages which are governed by either an inflammatory (M1) response or a tissue remodelling (M2) response. MicroRNA-223 has been implicated in inducing the polarization of M1 macrophages into M2 macrophages, effectively shifting an immune profile from pro-inflammatory to anti-inflammatory. We hypothesise that miR-223 contributes to the development of endometriosis by promoting an M2 response, resulting in persistence of endometriotic lesions. To address this hypothesis, a menstrual model of endometriosis in mice was established in miR-223 deficient mice. Donor ovariectomised mice were supplemented with oestrogen and progesterone to induce a ‘menstrual’ cycle. This ‘menstrual’ material was harvested and injected into a syngeneic recipient mouse. Endometriotic-like lesion development from transplanted tissue was measured at 1 and 2 weeks post tissue transfer. To address the contribution of miR-223, endometriotic-like lesions from miR-223-/- mice were compared to miR-223+/+. At one week following induction of endometriosis, miR-223-/- mice had endometriotic-like lesions that were 279% heavier (41.3mg vs 14.8mg) and 583% larger (100.3 mm3 vs 17.2 mm3) than miR-223+/+ mice. By day 14, lesion size and weight in both miR-223-/- and miR-223+/+ groups had significantly decreased (p<0.01) from week 1, indicative of immune activation to clear ectopic endometrial tissue. However, miR-223-/- mice lesions were again 210% heavier (8.05 mg vs 3.83mg) and 793% larger (19.83 mm3 vs 2.5 mm3) compared to miR-223+/+ mice. Collectively, these results suggest that miRNA-223 modulation of inflammatory responses during lesion development may result in reduced clearance of ectopic endometrial tissue.