Emerging evidence implicates that SIRT1, one of NAD-dependent protein deacetylase, is involved in the regulation of neuronal survival. However, the role of SIRT1 in mechanical injury is still unclear. Here, we first established a mechanical injury model of rat cortical neurons through exposing to 10 dyn/cm 2 laminar shear stress for 4 h. At the same time, we found that SIRT1 expression increased during the process of shear stress induced neuronal injury. SIRT1 overexpression in cortical neurons significantly decreased the percentage of died cells induced by shear stress. Our results demonstrate that SIRTl may play potential neuroprotective effects in shear stress induced mechanical injury.