Transforming growth factor-β 1 (TGFβ1) has a diverse role in astrogliosis and neuronal survival, but the underlying mechanism remains to be elucidated, especially in traumatic brain injury (TBI). Here, we show that the expression of TGFβ1 was increased in the pericontusional region, accompanied with astrogliosis and neuronal loss in TBI rats. Moreover, TGFβ1 knockdown not only reduced the number of neurons and inhibited astrogliosis but also resulted in a significant neurological dysfunction in rats with TBI. Subsequently, Smad3, a key downstream signal of TGFβ1, was involved in pericontusional region after TBI. These findings therefore indicate that TGFβ1 is involved in neuroprotection and astrogliosis, via activation of down stream Smad3 signal in the brain after injury.