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Here, conducting polyaniline (PANi) was used to construct a conductive guidance by coating on the surface of microtubes inserted in a three\u2010dimensional zein nerve conduit to study the repairing efficacy on peripheral nerve injury. PANi nanoparticles with a size of 20\u201330\u2009nm were synthesized and coated on the surface of microtubes through layer\u2010by\u2010layer deposition. Then, conduits including microtubes with and without PANi coating were implanted into rats to bridge a 10\u2010mm sciatic nerve defect and autograft as the control group. After 2 months, the conduit with PANicoating improved the recovery of proximal compound muscle action potential significantly in the regenerated nerve compared to the conduit without PANi coating, which was not inferior to the autograft group. However, the repairing efficacy was changed reversely at the fourth month postimplantation. PANi coating fragmented to form debris within or around the regenerated nerves while microtubes seem to degrade completely as observed by H&amp;E staining.<jats:italic>In vitro<\/jats:italic>degradation experiment confirmed this process. The PANi nanoparticles could induce cytotoxicity and reactive oxygen species (ROS) generation of both NIH 3T3 cells and macrophage cell line RAW 264.7. These<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>results implied that the nondegradable PANi may occupy the regeneration space and stimulate the inflammatory response in later implantation<jats:italic>in vivo<\/jats:italic>. While there was no such risk if the PANi coating keeps in an intact film. \u00a9 2019 Wiley Periodicals, Inc. 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