This review explores the emerging roles of lactate in acute and chronic inflammation, highlighting its complex and paradoxical effects on immune and inflammatory responses. Traditionally considered a waste product, lactate is now recognized as a crucial molecule involved in energy metabolism, signal transduction, and immune regulation. The discovery of lactylation, a post-translational modification, has further elucidated its regulatory role in inflammatory processes. Key enzymes such as hexokinase 2 (HK2), phosphofructokinase-1 (PFK-1), pyruvate kinase M2 (PKM2), and lactate dehydrogenase (LDH) play vital roles in lactate production and metabolism. Lactate affects immune cell function through specific receptors, including monocarboxylate transporters (MCTs) and sodium-coupled monocarboxylate transporters (SMCTs). The lactate/GPR81 pathway, involving GPR81 and arrestin β-2 (ARRB2), modulates inflammatory responses by inhibiting proinflammatory cytokine production. Additionally, lactate influences the polarization of macrophages from M1 to M2 phenotypes, promoting tissue repair and resolution of inflammation. In acute inflammation, lactate facilitates energy production and immune cell activation, while in chronic inflammation, it can amplify and persist inflammatory responses. Lactylation, a post-translational modification, regulates gene expression and macrophage polarization, contributing to tissue damage and disease progression. The review also discusses the therapeutic potential of lactate-related interventions, such as targeting lactate transporters and lactylation pathways, to manage inflammation-related diseases.This review explores the emerging roles of lactate in acute and chronic inflammation, highlighting its complex and paradoxical effects on immune and inflammatory responses. Traditionally considered a waste product, lactate is now recognized as a crucial molecule involved in energy metabolism, signal transduction, and immune regulation. The discovery of lactylation, a post-translational modification, has further elucidated its regulatory role in inflammatory processes. Key enzymes such as hexokinase 2 (HK2), phosphofructokinase-1 (PFK-1), pyruvate kinase M2 (PKM2), and lactate dehydrogenase (LDH) play vital roles in lactate production and metabolism. Lactate affects immune cell function through specific receptors, including monocarboxylate transporters (MCTs) and sodium-coupled monocarboxylate transporters (SMCTs). The lactate/GPR81 pathway, involving GPR81 and arrestin β-2 (ARRB2), modulates inflammatory responses by inhibiting proinflammatory cytokine production. Additionally, lactate influences the polarization of macrophages from M1 to M2 phenotypes, promoting tissue repair and resolution of inflammation. In acute inflammation, lactate facilitates energy production and immune cell activation, while in chronic inflammation, it can amplify and persist inflammatory responses. Lactylation, a post-translational modification, regulates gene expression and macrophage polarization, contributing to tissue damage and disease progression. The review also discusses the therapeutic potential of lactate-related interventions, such as targeting lactate transporters and lactylation pathways, to manage inflammation-related diseases.