Abstract： Objective To observe the changes of Na(v)1.6 expression in rats after acute cerebral ischemia and the effect of Riluzole (the sodium channel blocker) on these changes, and discuss the relationship between level of Na(v)l.6 and cerebral ischemia. Methods One hundred and five healthy SD rats were randomly divided into sham-operated group (n=15), ischemia control group (IC, n=45) and Riluzole therapy group (RT, n=45). Rat models of focal acute cerebral ischemia in the later 2 groups were established by permanent occlusion of right middle cerebral artery. Riluzole at a dosage of 8 mg/kg was given once daily to the rats of the RT group 30 min after ischemia. Tissues from the striatum were collected at different time points (6 h, and 1, 2, 3 and 7 d after ischemia); the expressions of Na(v)1.6 in the striatum were detected by immunofluorescence staining and real-time quantitative PCR at each time point; and the infarct volume was observed by triphenyltetrazolium chloride staining at each time point.Results The rats in the IC group and RT group showed neurologic impairment, especially 2 d after ischemia; rats of the IC group presented significantly higher scores of neurological function scale than those of the RT group at the same time point (P＜0.05). Immunofluorescence staining showed that the expression of Na (v)1.6 was up-regulated, and reached its peak level 1 d after ischemia but then, was down-regulated both in the IC group and RT group. Real-time quantitative PCR showed that the expression of Na(v)1.6 in the IC group was up-regulated 1 d after ischemia, and then down-regulated 2, 3 and 7 d after ischemia, however, that in the RT group was down-regulated 6 h after ischemia; the mRNA expression of Na (v)1.6 in the RT group was obviously down-regulated as compared with that in the IC group at the same time point (P＜0.05). The infarction volume became the largest 3 daRer ischemia both in the IC group and RT group; the infarction volume in RT group was smaller than that in IC group at the same time point (P＜0.05). Conclusion The expression of Na(v)1.6 is down-regulated after cerebral ischemic injury to mitigate acute cerebral ischemic injury, indicating that Na (v)1.6 might involve in the development of cerebral ischemic injury.