Unlike mammals, adult zebrafish efficiently regenerate functional nervous system tissue after major spinal cord injury. Whereas glial scarring is a major roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue and facilitate regeneration, a process about which little is known. Here, we performed a genome-wide profiling screen for secreted factors that are induced during zebrafish spinal cord regeneration. We find that connective tissue growth factor a (ctgfa) is induced in and around the glial cells that participate in initial bridging events. Mutations in ctgfa permit development to adulthood but disrupt spinal cord repair, whereas transgenic ctgfa overexpression and local recombinant protein delivery accelerate bridging and functional regeneration. Our study reveals Ctgf as a pro-regenerative factor that is necessary and sufficient to stimulate glial bridging and natural spinal cord regeneration.