The inflammatory response following stroke is a critical factor in the progression of ischemic brain injury. This review discusses the role of systemic and local inflammation in experimental stroke, focusing on the contributions of various cell types, inflammatory signaling pathways, and mediators. Stroke leads to cerebral ischemia, which triggers an inflammatory response involving leukocytes, endothelium, glia, microglia, and the extracellular matrix. This response includes the activation of inflammatory signaling pathways such as nuclear factor kappa beta (NF-κB) and mitogen-activated protein kinases (MAPK), as well as the production of cytokines, chemokines, reactive oxygen species (ROS), and arachidonic acid metabolites. These inflammatory mediators contribute to secondary injury, including brain edema, microvascular stasis, and blood-brain barrier (BBB) disruption, which can lead to further brain damage. Leukocytes, particularly neutrophils, play a significant role in the inflammatory response, contributing to secondary injury through the release of proinflammatory mediators. Microglia and macrophages also contribute to the inflammatory response, with their activation leading to the release of cytotoxic agents that can damage brain tissue. Astrocytes, traditionally considered non-inflammatory, can also become activated and contribute to inflammation by expressing inflammatory mediators and participating in the immune response. Adhesion molecules, such as selectins, immunoglobulin superfamily members, and integrins, are crucial in the infiltration of leukocytes into the brain parenchyma following stroke. Inhibiting these adhesion molecules can reduce neurologic injury. Inflammatory mediators such as cytokines (e.g., IL-1, TNF-α, IL-6, IL-10, TGF-β), chemokines, and arachidonic acid metabolites play significant roles in the inflammatory response. These mediators can exacerbate brain injury or, in some cases, have neuroprotective effects. The transcriptional regulation of inflammation, particularly through NF-κB and MAPK pathways, is also critical in the inflammatory response following stroke. These pathways are involved in the activation of inflammatory genes and the production of inflammatory mediators. The role of these pathways in stroke is complex, with some studies suggesting protective effects and others indicating harmful outcomes. Overall, the inflammatory response following stroke is a multifaceted process involving various cell types, signaling pathways, and mediators. Understanding these mechanisms is essential for developing therapeutic strategies to reduce the extent of brain injury and improve outcomes in stroke patients.The inflammatory response following stroke is a critical factor in the progression of ischemic brain injury. This review discusses the role of systemic and local inflammation in experimental stroke, focusing on the contributions of various cell types, inflammatory signaling pathways, and mediators. Stroke leads to cerebral ischemia, which triggers an inflammatory response involving leukocytes, endothelium, glia, microglia, and the extracellular matrix. This response includes the activation of inflammatory signaling pathways such as nuclear factor kappa beta (NF-κB) and mitogen-activated protein kinases (MAPK), as well as the production of cytokines, chemokines, reactive oxygen species (ROS), and arachidonic acid metabolites. These inflammatory mediators contribute to secondary injury, including brain edema, microvascular stasis, and blood-brain barrier (BBB) disruption, which can lead to further brain damage. Leukocytes, particularly neutrophils, play a significant role in the inflammatory response, contributing to secondary injury through the release of proinflammatory mediators. Microglia and macrophages also contribute to the inflammatory response, with their activation leading to the release of cytotoxic agents that can damage brain tissue. Astrocytes, traditionally considered non-inflammatory, can also become activated and contribute to inflammation by expressing inflammatory mediators and participating in the immune response. Adhesion molecules, such as selectins, immunoglobulin superfamily members, and integrins, are crucial in the infiltration of leukocytes into the brain parenchyma following stroke. Inhibiting these adhesion molecules can reduce neurologic injury. Inflammatory mediators such as cytokines (e.g., IL-1, TNF-α, IL-6, IL-10, TGF-β), chemokines, and arachidonic acid metabolites play significant roles in the inflammatory response. These mediators can exacerbate brain injury or, in some cases, have neuroprotective effects. The transcriptional regulation of inflammation, particularly through NF-κB and MAPK pathways, is also critical in the inflammatory response following stroke. These pathways are involved in the activation of inflammatory genes and the production of inflammatory mediators. The role of these pathways in stroke is complex, with some studies suggesting protective effects and others indicating harmful outcomes. Overall, the inflammatory response following stroke is a multifaceted process involving various cell types, signaling pathways, and mediators. Understanding these mechanisms is essential for developing therapeutic strategies to reduce the extent of brain injury and improve outcomes in stroke patients.