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We searched PubMed, Cochrane Library, ClinicalTrials.gov, Scopus, Embase, and Google Scholar. Available evidence demonstrates increased macrophage accumulation and substantial heterogeneity across the eutopic endometrium, peritoneal fluid, and established endometriotic lesions. Rather than undergoing a uniform shift from an M1 to an M2 phenotype, endometriosis\u2010associated macrophages acquire overlapping inflammatory, immunoregulatory, angiogenic, phagocytic, metabolic, and profibrotic programs. Endometriotic epithelial and stromal cells regulate macrophage recruitment and activation through estrogen receptor \u03b2\u2013NF\u2010\u03baB\u2013CCL2 signaling, IL\u201017A\u2010 and TNF\u2010\u03b1\u2010dependent cytokine production, extracellular\u2010vesicle\u2010mediated microRNA transfer, and lactate\u2010driven METTL3\u2013Trib1\u2013ERK\/STAT3 signaling. The CCL2\/MCP\u20101\u2013CCR2 axis further links monocyte recruitment with inflammatory signaling and the invasive behavior of endometriotic cells, whereas TET3\u2010mediated suppression of let\u20107 microRNAs sustains disease\u2010associated macrophage activation. Functionally, macrophages contribute to defective clearance of displaced endometrial tissue, ectopic cell survival, angiogenesis, fibrosis, neuroimmune sensitization, pain, and impaired reproductive function. These findings support an immunometabolic model in which macrophage plasticity drives lesion establishment, progression, neuroangiogenesis, pain, and infertility. Therapeutically, targeting macrophage polarization and metabolism\u2014via glycolytic and mitochondrial pathways, lactate signaling, or epitranscriptomic regulators\u2014may restore immune homeostasis and limit disease progression. Further translational studies are needed to validate biomarkers and develop macrophage\u2010directed interventions.<\/jats:p>","DOI":"10.1111\/aji.70331","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:38:39Z","timestamp":1791985119000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage Polarization and Metabolic Reprogramming in Endometriosis: Mechanisms and Therapeutic Implications"],"prefix":"10.1111","volume":"96","author":[{"given":"Leila","family":"Adamyan","sequence":"first","affiliation":[{"name":"Federal State Budgetary Educational Institution of Higher Education \u201cRussian University of Medicine\u201d of The Ministry of Health of The Russian Federation  Moscow Russia"},{"name":"National Medical Research Center for Obstetrics Gynecology and Perinatology Named After Academician V.I. 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