Accumulating evidence has shown that the central nervous system can mount a well-defined inflammatory reaction to a variety of insults including trauma, ischemia, transplantation, viral infection, and immune and neurodegenerative disorders. In this review, we summarize the evidence that in brain ischemia and trauma, inflammatory reaction figures prominently in mediation of brain injury. The inflammatory condition consists of inflammatory cells (first neutrophils, followed by monocytes/macrophages) and mediators (cytokines, chemokines and adhesion molecules). De novo up-regulation of various inflammatory mediators has been observed and their roles in brain injury have been extensively studied. In addition, recent evidence emerges on specific signal pathways in brain injury. Taken together, targeting specific inflammatory mediators involved in brain injury may provide novel therapeutic opportunities for CNS injury such as stroke and neurotrauma.