The contribution of single complement system (CS) activation pathways to cerebral IR injury has not yet been adequately studied after ischemic stroke and reperfusion. It remains unclear whether a specific activation pathway (alternative, classical or lectin), single complement factors within the CS, or anaphylatoxins are responsible for increased cerebral IR injury after ischemic stroke and reperfusion. Also poorly understood is the relationship between these elements (activation pathways, CS factors and anaphylatoxins) and neutrophil mediated cerebral IR injury. The objective of this dissertation was to test the hypothesis that mannose binding lectin (MBL) deficiency during cerebral ischemia and reperfusion will result in a significant reduction of systemic neutrophil activation and cerebral injury after ischemic stroke and reperfusion via decreased CS activation and subsequent decreased anaphylatoxin production. Using the intraluminal filament method, mice with targeted mutations to MBL A/C genes (MBL-/- ) or the C57Bl/6 strain (MBL +/+ ) were subjected to 60 minutes of cerebral ischemia and either 15 minutes or 24 hours of reperfusion. After reperfusion (15 min and 24 hour) blood was removed to assess systemic neutrophil CD11b expression via flow cytometry. After 24 hours of reperfusion, the brain was removed to assess cerebral injury. CS activation after ischemic stroke and reperfusion was assessed via immunofluorescent C3 staining and RT-rtPCR methods. Our primary findings are, after ischemic stroke and reperfusion: (1) hepatic MBLA gene expression is significantly increased, (2) systemic neutrophils significantly express CD11b, (3) MBL deficiency significantly decreased cerebral infarct volume in the striatum but not in the cortex or total hemisphere, and (4) systemic neutrophil activation is independent of MBL deficiency. This study is the first to examine the contribution of MBL-initiated lectin pathway activation to cerebral IR injury after ischemic stroke and reperfusion. These findings suggest that MBL deficiency does not significantly reduce neutrophil activation or protect brain tissue after ischemic stoke and reperfusion. A complete understanding of reperfusion events after ischemic stroke is necessary for successful development of future stroke therapies to prevent cerebral IR injury. In this way, the acquisition of knowledge from the bench serves the stroke population cared for by nurses at the bedside.