We investigated the role of laminin in functional recovery of a peripheral nerve injury using electrophysiological and behavioral approaches on the rat sciatic nerve in vivo. These studies were complemented by neurofilament protein immunocytochemistry on the sciatic nerve 20 days after an operation, in which an 8-mm piece of the nerve was removed and replaced by a graft of laminin, its neurite outgrowth-promoting peptide, a control peptide, collagen, or by resuturing of the removed piece of the nerve. Electrophysiological measurements of muscle strength 4 months after the sciatic nerve transection showed that a laminin graft was as effective as neurorrhaphy in supporting functional recovery of an injured peripheral nerve. A laminin graft also significantly reduced autotomy in the operated animals. Immunocytochemistry confirmed that both a laminin graft and resuturing supported growth of the 200-kDa neurofilament-positive axons into the distal stump of the nerve within 20 days of operation. A graft with a neurite outgrowth-promoting peptide of the B2 chain of laminin supported similar axon growth, whereas another peptide graft also derived from laminin or a collagen graft did not support axon growth. All grafts allowed Schwann cell growth into the distal stumps of the nerves, but neurites accompanied them only in the regeneration-supporting grafts and in the resutured nerves. The Schwann cells of the regenerating nerves expressed high levels of the neurite outgrowth-promoting domain of the B2 chain of laminin, whereas the Schwann cells of the degenerating nerves failed to express this domain in the distal stumps of the degenerating nerves. These results provide the first in vivo evidence for the functional role of laminin in peripheral nerve regeneration. As the neurite outgrowth-promoting domain of the B2 chain of laminin is as efficient as laminin or resuturing in supporting a short-term recovery of an injured sciatic nerve, this area may be a regeneration-promoting domain of this glycoprotein. More importantly, as grafting significantly reduces post-traumatic pain behavior in the operated animals, the laminin graft surgery may provide a useful method for clinical restoration of the injured peripheral nerves.