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Defensins are small cationic peptides that constitute the first line of defense against pathogens and are involved in immune regulation. In this study, their role in peripheral nerve regeneration was investigated. Rat sciatic nerves were transected and the two nerve stumps were bridged by a chitin conduit with a gap of 5mm between the stumps. The animals were injected intramuscularly with mutated rabbit neutrophil peptide 1 (defensin mNP-1), the positive control nerve growth factor (NGF) or the negative control saline, for 7 consecutive days after repair. After 6 weeks, the sciatic functional index (SFI), MNCV (motor nerve conductive velocity) and morphological parameters including myelinated fiber amounts, fiber diameter, axon diameter, myelin thickness and G-ratio were measured. Compared to the SFI of saline group, the NGF and mNP-1 groups had an increase of 18.3% and 18.8%, respectively. The numbers of myelinated fibers in the distal nerve of NGF and mNP-1 groups were 1.45- and 1.32-fold higher than in the saline group. The MNCVs of NGF and mNP-1 groups were 7.3 and 4.4 times of that of saline group. Fiber diameter, axon diameter, myelin thickness and G-ratio in the NGF and mNP-1 groups were also significantly higher than those of saline group. Our results demonstrate that, like NGF, the defensin mNP-1 can promote regeneration after a peripheral nerve cut., (Copyright © 2016. Published by Elsevier Ireland Ltd.)