The article reviews the molecular mechanisms underlying the polarization of macrophages into M1 and M2 phenotypes. Macrophages, key components of the innate immune system, can differentiate into distinct functional phenotypes in response to various environmental cues. M1 macrophages are activated by microbial products or pro-inflammatory cytokines, characterized by high antigen presentation, production of IL-12 and IL-23, and increased production of nitric oxide (NO) and reactive oxygen intermediates (ROI). In contrast, M2 macrophages are "resting" phenotypes observed during healing processes without infections, characterized by upregulation of various receptors and the production of ornithine and polyamines through the arginase pathway. The polarization of macrophages is regulated by various inflammatory modulators, signaling molecules, and transcription factors, including the IRF/STAT signaling pathway, which is central to modulating macrophage polarization. The article also discusses the role of microRNAs (miRNAs) in regulating macrophage polarization, highlighting their ability to modulate gene expression at the posttranscriptional level. Additionally, the article explores the influence of hypoxia-inducible factors (HIFs), NOD-like receptors (NLRs), granulocyte-macrophage colony-stimulating factor (GM-CSF), and lincRNAs on macrophage polarization. The dynamic nature of macrophage polarization and the potential therapeutic implications of targeting imbalances in macrophage polarization are also discussed.The article reviews the molecular mechanisms underlying the polarization of macrophages into M1 and M2 phenotypes. Macrophages, key components of the innate immune system, can differentiate into distinct functional phenotypes in response to various environmental cues. M1 macrophages are activated by microbial products or pro-inflammatory cytokines, characterized by high antigen presentation, production of IL-12 and IL-23, and increased production of nitric oxide (NO) and reactive oxygen intermediates (ROI). In contrast, M2 macrophages are "resting" phenotypes observed during healing processes without infections, characterized by upregulation of various receptors and the production of ornithine and polyamines through the arginase pathway. The polarization of macrophages is regulated by various inflammatory modulators, signaling molecules, and transcription factors, including the IRF/STAT signaling pathway, which is central to modulating macrophage polarization. The article also discusses the role of microRNAs (miRNAs) in regulating macrophage polarization, highlighting their ability to modulate gene expression at the posttranscriptional level. Additionally, the article explores the influence of hypoxia-inducible factors (HIFs), NOD-like receptors (NLRs), granulocyte-macrophage colony-stimulating factor (GM-CSF), and lincRNAs on macrophage polarization. The dynamic nature of macrophage polarization and the potential therapeutic implications of targeting imbalances in macrophage polarization are also discussed.