AbstractAcellular nerves possess the structural and biochemical features similar to those of naive endoneurial tubes, and have been proved bioactive for allogeneil graft in nerve tissue engineering. However, the source of allogenic donators is restricted in clinical treatment. To explore sufficient substitutes for acellular nerve allografts (ANA), we investigated the effectiveness of acellular nerve xenografts (ANX) combined with bone marrow stromal cells (BMSCs) on repairing peripheral nerve injuries. The acellular nerves derived from Sprague‐Dawley rats and New Zealand rabbits were prepared, respectively, and BMSCs were implanted into the nerve scaffolds and cultured in vitro. All the grafts were employed to bridge 1 cm rat sciatic nerve gaps. Fifty Wistar rats were randomly divided into five groups (n = 10 per group): ANA group, ANX group, BMSCs‐laden ANA group, BMSCs‐laden ANX group, and autologous nerve graft group. At 8 weeks post‐transplantation, electrophysiological study was performed and the regenerated nerves were assayed morphologically. Besides, growth‐promoting factors in the regenerated tissues following the BMSCs integration were detected. The results indicated that compared with the acellular nerve control groups, nerve regeneration and functional rehabilitation for the xenogenic nervetransplantation integrated with BMSCs were advanced significantly, and the rehabilitation efficacy was comparable with that of the autografting. The expression of neurotrophic factors in the regenerated nerves, together with that of brain‐derived neurotrophic factor (BDNF) in the spinal cord and muscles were elevated largely. In conclusion, ANX implanted with BMSCs could replace allografts to promote nerve regeneration effectively, which offers a reliable approach for repairing peripheral nerve defects. Synapse, 2012. © 2011 Wiley Periodicals, Inc.