Macrophages, as key components of innate immunity, exhibit diverse and plastic functions in both promoting and inhibiting cell proliferation and tissue repair. They can be classified into two main activation states: M1 and M2, which mirror the Th1-Th2 polarization of T cells. M1 macrophages are pro-inflammatory, releasing cytokines that inhibit cell proliferation and damage tissue, while M2 macrophages are anti-inflammatory, promoting tissue repair and immune tolerance. The balance between M1 and M2 polarization is tightly regulated by signaling pathways, transcriptional and post-transcriptional networks, and is crucial for maintaining homeostasis. Imbalances in this balance are associated with various diseases and inflammatory conditions. The M1-M2 polarization of macrophages is influenced by multiple factors, including signaling pathways such as IRF/STAT, TLR, NLR, and SOCS, as well as microRNAs (miRNAs). For example, IRF/STAT signaling is central to macrophage polarization, with STAT1 promoting M1 polarization and STAT3/STAT6 promoting M2 polarization. TLR signaling, particularly through TLR4, drives macrophages toward an M1 phenotype, while IL-4, IL-10, and IL-13 promote M2 polarization. miRNAs such as miR-155 and miR-223 also play roles in modulating macrophage polarization by targeting specific genes. Macrophage polarization is also influenced by the microenvironment, including hypoxia, which can shift macrophages from an M1 to an M2 phenotype. Additionally, the NOD-like receptors (NLRs) and the inflammasome play roles in pro-inflammatory responses, while the HIF-1α and HIF-2α pathways regulate macrophage metabolism and function under hypoxic conditions. The polarization of macrophages is dynamic and can be reversed under physiological or pathological conditions. This plasticity is regulated by various transcription factors, including PPARγ, KLF-4, and IRF4, which are involved in promoting M2 polarization. Additionally, miRNAs such as miR-155 and miR-223 are involved in modulating macrophage polarization by targeting genes involved in inflammation and immune responses. Understanding the molecular mechanisms underlying macrophage polarization is essential for developing therapeutic strategies for diseases involving macrophage dysfunction. This includes targeting imbalances in macrophage polarization to treat conditions such as cancer, inflammation, and autoimmune diseases. Future research should focus on identifying new molecules and pathways that regulate macrophage polarization, as well as exploring the role of non-coding RNAs like lincRNAs in this process.Macrophages, as key components of innate immunity, exhibit diverse and plastic functions in both promoting and inhibiting cell proliferation and tissue repair. They can be classified into two main activation states: M1 and M2, which mirror the Th1-Th2 polarization of T cells. M1 macrophages are pro-inflammatory, releasing cytokines that inhibit cell proliferation and damage tissue, while M2 macrophages are anti-inflammatory, promoting tissue repair and immune tolerance. The balance between M1 and M2 polarization is tightly regulated by signaling pathways, transcriptional and post-transcriptional networks, and is crucial for maintaining homeostasis. Imbalances in this balance are associated with various diseases and inflammatory conditions. The M1-M2 polarization of macrophages is influenced by multiple factors, including signaling pathways such as IRF/STAT, TLR, NLR, and SOCS, as well as microRNAs (miRNAs). For example, IRF/STAT signaling is central to macrophage polarization, with STAT1 promoting M1 polarization and STAT3/STAT6 promoting M2 polarization. TLR signaling, particularly through TLR4, drives macrophages toward an M1 phenotype, while IL-4, IL-10, and IL-13 promote M2 polarization. miRNAs such as miR-155 and miR-223 also play roles in modulating macrophage polarization by targeting specific genes. Macrophage polarization is also influenced by the microenvironment, including hypoxia, which can shift macrophages from an M1 to an M2 phenotype. Additionally, the NOD-like receptors (NLRs) and the inflammasome play roles in pro-inflammatory responses, while the HIF-1α and HIF-2α pathways regulate macrophage metabolism and function under hypoxic conditions. The polarization of macrophages is dynamic and can be reversed under physiological or pathological conditions. This plasticity is regulated by various transcription factors, including PPARγ, KLF-4, and IRF4, which are involved in promoting M2 polarization. Additionally, miRNAs such as miR-155 and miR-223 are involved in modulating macrophage polarization by targeting genes involved in inflammation and immune responses. Understanding the molecular mechanisms underlying macrophage polarization is essential for developing therapeutic strategies for diseases involving macrophage dysfunction. This includes targeting imbalances in macrophage polarization to treat conditions such as cancer, inflammation, and autoimmune diseases. Future research should focus on identifying new molecules and pathways that regulate macrophage polarization, as well as exploring the role of non-coding RNAs like lincRNAs in this process.