Chitooligosaccharides (COSs) are the biodegradation products of chitosan that have been demonstrated with neuroaffinity and/or neuroprotective actions. In this study, we investigated the possible benefits of treatment with COSs on nerve regeneration after crush injuries to peripheral nerves. The rabbits with the crushed common peroneal nerve were treated by daily intravenous injection of 1.5 or 3 mg/kg body weight of COSs or identical volume of saline (as the control) for a 6-week period. At the end of COSs treatment, electrophysiological assessments, Meyer's trichrome and Masson trichrome staining, and transmission electron microscopy were used to evaluate the regeneration of injured common peroneal nerve and atrophy of the tibialis posterior muscle. The results showed that the compound muscle action potentials, the number of regenerated myelinated nerve fibers, the thickness of regenerated myelin sheaths, and the cross-sectional area of tibialis posterior muscle fibers were significantly improved in the nerves that received COSs treatment and the results with COSs treatment displayed a dose-dependent pattern. This study demonstrated that COSs accelerated peripheral nerve regeneration after crush injury to rabbit common peroneal nerves. The COSs could probably become a potential neuroprotective agent for improvement of peripheral nerve regeneration after the injury and deserve for further studies.