This chapter reviews the inflammatory response in stroke, focusing on the contributions of systemic and local inflammation. It discusses the roles of various cell types, including leukocytes, endothelium, glia, microglia, and neurons, as well as extracellular matrix and neurons. The chapter also examines intracellular inflammatory signaling pathways such as nuclear factor kappa beta and mitogen-activated protein kinases, and mediators produced by inflammatory cells like cytokines, chemokines, reactive oxygen species, and arachidonic acid metabolites. The potential for therapy in stroke and hypoxic-ischemic injury is explored, highlighting the importance of understanding and targeting these inflammatory processes to reduce brain damage and improve outcomes.This chapter reviews the inflammatory response in stroke, focusing on the contributions of systemic and local inflammation. It discusses the roles of various cell types, including leukocytes, endothelium, glia, microglia, and neurons, as well as extracellular matrix and neurons. The chapter also examines intracellular inflammatory signaling pathways such as nuclear factor kappa beta and mitogen-activated protein kinases, and mediators produced by inflammatory cells like cytokines, chemokines, reactive oxygen species, and arachidonic acid metabolites. The potential for therapy in stroke and hypoxic-ischemic injury is explored, highlighting the importance of understanding and targeting these inflammatory processes to reduce brain damage and improve outcomes.