Objective To explore the feasibility of combining chitosan conduit filled with simvastatin/pluronic F-127 thermosensitive hydrogel to repair peripheral nerve defects in rats. Methods The chitosan conduits and simvastatin/pluronic F-127 hydrogel were prepared and tested by stereomicroscope, SEM, vitro degradation testing and rheometer property. A total of 40 Sprague-Dawley rats were randomly divided into 4 groups (n=10 per group): the chitosan conduit alone (conduit group) or the conduit filled with pluronic F-127 hydrogel containing 0 (c+sim 0mg), 0.5 (c+sim 0.5mg), and 1 mg (c+sim 1mg) simvastatin. A 10mm nerve defect was created in the rat left sciatic nerve and bridged with the chitosan conduit filled with pluronic F-127 hydrogel containing different doses of simvastatin. At 10 weeks after surgery, the regenerated nerves were performed the H&E and TEM to observe the morphological change. The diameters of the myelinated axons, the thickness of the myelin sheath, and the G-ratios (the ratio of the axon diameter to the total fiber diameter) were calculated to make statistical analyses. And the immunohistochemical method was used to measure the expression of NF200 and S100 protein in the regenerated nerves and to detect the expression of neurotrophins including pleiotrophin (PTN), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF). Results The chitosan conduits filled with simvastatin/pluronic F-127 promote nerve regeneration in rats. All groups showed the regenerated nerves, but H&E staining showed that the regenerated nerves in the simvastatin treated groups were much thicker than those without simvastatin; And the same trend was also found for the diameter of the myelinated axons, the thickness of the myelin sheath and G-ratio; In addition, the numbers of NF-positive cells indicating regenerated axons and S100-positive cells indicating Schwann cells were significantly larger in simvastatin treated groups than those without simvastatin. And immunohistochemical staining indicated that simvastatin induced an increased expression of PTN, HGF, VEGF and GDNF compared to those found in the control group. Conclusions Taken together, the simvastatin/pluronic F-127 hydrogel filling in the chitosan conduits promoted the reconstruction of histological in peripheral nerve defects, which can be used for peripheral nerve regeneration.