Thyroid hormone plays an important role in regulating the development and regeneration of the nervous system. Our previous work showed that local administration of triiodothyronine (T3) at the level of transected rat sciatic nerve increased the number and diameter of regenerated axons, but the mechanism underlying the improved regeneration is still unclear. Here, we have investigated the effect of T3 on the expression of SCG10, a regulator of microtubule dynamics in growth cones. After transection of adult rat sciatic nerves, silicone tubes were implanted and filled with T3 or phosphate-buffered solution. At various time points following surgery, the expression of SCG10 protein and mRNA was analyzed. Semi-quantitative Western blot analysis revealed that sciatic nerve transection induced a more than 20-fold upregulation of SCG10 protein in proximal nerve segments at 1 day post-lesion, while at this time point, SCG10 mRNA in dorsal root ganglion neurons was not increased yet. The increase in SCG10 protein and mRNA could be observed over 30 days. Local T3 treatment significantly enhanced the increase in SCG10 protein levels about two-fold in the different segments of transected nerve during the regeneration period. Also SCG10 mRNA levels in lumbar ganglia were enhanced. Immunohistochemical analysis showed that T3 treatment not only increased the number of SCG10 positive axons but also the intensity of their staining. These results suggest that SCG10 is involved in the regulation of regeneration. The stimulating effect of T3 on SCG10 expression could provide a mechanism by which T3 enhances peripheral nerve regeneration.