Traumatic brain injury (TBI) triggers neuronal death mechanisms that significantly induce neuronal loss and neurological dysfunction. Our previous study revealed that Sirt1 could improve the neuroprotective effect by reducing the astrocyte activation after TBI. Nevertheless, the underlying mechanisms of Sirt1 attenuating astrocyte activation still remain unclear. The following study examined whether the protection of Sirt1 in nigrostriatal pathway injury is associated with autophagy regulation. We established a nigrostriatal pathway injury in the mouse brain in order to mimic the traumatic brain injury and up-regulated Sirt1 expression by resveratrol. Consequently, we analyzed the effect of Sirt1 up-regulation on LC3 and monitored the LC3 localization in the astrocytes, microglial cells and neurons. We found that the Sirt1 up-regulation by resveratrol increased the expression of LC3 around the lesion site after injury. Confocal results showed that Sirt1 up-regulation increased the expression of LC3 in astrocytes and decreased the expression in the neurons, while low effect was found on the microglial cells. Moreover, compared the resveratrol treatment groups, a typical nucleocytoplasmic localization with strong distribution in the nucleus (in astrocyte and neurons) was observed in the control group (treated with DMSO). To sum up, our data suggested that regulation of Sirt1 expression could enhance autophagy in the astrocytes and decrease the expression in the neurons. This mechanism, which may probably relate to the distribution of LC3 in cytoplasm and nucleus, provides a new theoretical basis for exploring the neuroprotective mechanism of Sirt1 after brain injury.