Three-dimensional biocompatible and biodegradable scaffolds play important roles in tissue engineering. In this study, fibrous mats composed of electrospun poly(epsilon-caprolactone) (PCL)/small intestine submucosa (SIS) tubes were fabricated with a high degree of longitudinal alignment as a conduit for peripheral nerves. Fourier transform infrared analyses of electrospun PCL/SIS mats with various amounts of SIS showed that the SIS was well embedded within the PCL matrix. The diameter of the PCL/SIS fibers with the 3 wt % of SIS in the PCL solution decreased 40% relative to that of pure PCL fibers due to increased electrical conductivity and decreased surface tension. PCL/SIS (3 wt %) electrospun mats exhibited various synergistic effects, including stronger mechanical properties (Young's modulus = more than 80%) and enhanced hydrophilicity (water contact angle at 30 min = 54 degrees ) relative to pure PCL (water contact angle at 30 min = 142 degrees ). Cell attachment and proliferation experiments demonstrated that the interactions between nerve cells (PC-12) and the PCL/SIS conduits were more favorable than those between PC-12 cells and a pure PCL conduit. This study contributes to the understanding of the effects of including SIS in electrospun composite mats. The ability to fabricate highly aligned tubes of PCL/SIS with appropriate mechanical properties and cellular interactions shows great potential for the design of nerve regeneration conduits.