Natto is a traditional Japanese food prepared from fermented soybeans. nattokinase (NK) is considered one of the most active functional ingredients in natto. The present study evaluated the neuroprotective effects of NK in gerbils subjected to focal cerebral ischemia. The gerbils were separated into four groups: control group, ischemic group and two NK groups (4 and 40 mg/day i.g. for 7 days). All gerbils were fed standard chow with or without NK prior to cerebral ischemia. Focal cerebral ischemia was induced by the occlusion of the right common carotid artery and middle cerebral artery for 60 min, followed by reperfusion. Infarct volumes were determined by 2, 3, 5-triphenyltetrazolium chloride staining. Anti-thrombotic effects of NK, such as fibrinogen, prothrombin time and activated partial thromboplastin time, were also determined. Our data showed that NK significantly reduced infarct volumes by 54-68% (p < 0.01), compared to the ischemic group. Prothrombin time was not significantly different in all groups. However, low dosage NK (4 mg/day) reversed ischemic-induced increase in fibrinogen concentrations and activated partial thromboplastin time. In summary, the data indicated that oral intake of NK for 7 days may alter fibrinolytic activity and provide neuroprotective effects against focal cerebral ischemia in gerbils.