Trauma to the spinal cord initiates a series of cellular and biochemical processes that damage both neurons and glia. TGF-beta and its receptors are expressed around the injury site following a spinal cord injury. Here, we report that the intrathecal administration of a neutralizing antibody to TGF-beta1 in rats with thoracic spinal cord contusion results in a significant enhancement of the locomotor recovery. The inhibition of TGF-beta1 suppresses glial scar formation and upregulates microglia/macrophage activation after the injury, presumably providing a favorable environment for restoration of the neural network. Rats treated with the anti-TGF-beta1 antibody exhibited a mild enhancement of growth and/or preservation of axons in the injured spinal cord caudal to the site of contusion. These results support the possibility of using TGF-beta1 inhibitors in the treatment of human spinal cord injuries.