We investigated the effects of a novel carboxymethylcellulose (CMC)-derived hydrogel, in which phosphatidylethanolamine (PE) was introduced into the carboxyl groups of CMC, for preventing perineural adhesion after extensive internal neurolysis of rat sciatic nerve. Sciatic nerves were randomly assigned to one of the following groups: the Control group, operated but no treatment; the HA group, operated and treated with 1% hyaluronan; the CMC-PE(L) group, operated and treated with low-viscosity CMC-PE hydrogel; and the CMC-PE(H) group, operated and treated with high-viscosity CMC-PE hydrogel. Perineural adhesions were evaluated at 6 weeks. Nerves were also subjected to biomechanical testing to assess ultimate breaking strength. Electrophysiological and wet muscle weight measurements were performed. Breaking strengths were significantly lower for the CMC-PE(L) group than for the Control and HA groups. Latency was significantly longer for the Control group than for the CMC-PE(L) group at 20 days. The mean percentage of wet muscle weight to body weight was significantly lower for the Control group than for the CMC-PE(L) group at 6 weeks. Low-viscosity CMC-PE hydrogel appears to prevent perineural adhesions and allow early restoration of nerve function.