Abstract: Objective To investigate whether heme oxygenase-1（HO-1） could enhance the immunosuppressive effects of bone marrow mesenchymal stem cells（BMMSC）on the rejection of transplanted small bowel allograft in rats. Methods The rejection model of ectopic small bowel transplantation in rats was established，then BMMSC or HO-1/BMMSC were transfused via the dorsal penis vein. The histopathological changes of the transplanted small bowel and the change of regulatory T cell（Tregs），natural killer cell（NK）and cytokines after transplantation were observed in different groups. Results The acute rejection model rats after small bowel transplantation showed mild to moderate on post operation day 5（POD5）and severe acute rejection on POD7. BMMSC showed strong protective effects on rejection within the first 7 days after transplantation，anda downward trend since POD10. While HO-1/BMMSC showed stronger effects than BMMSC，which provided enhanced protective effects on the transplanted small bowel. In addition，the activity of natural killer（NK） cell decreased significantly，the levels of regulatory T cells（Tregs），interleukin-10（IL-10）and transforming growth factor-β（TGF-β） increased significantly， and the levels of interleukin-2（IL-2）， interleukin-6 （IL-6），interleukin-17（IL-17），interleukin-23（IL-23），tumor necrosis factor -α（TNF-α）and interferon-γ （IFN-γ）decreased significantly in the HO-1/BMMSC group， when compared with the BMMSC group. Conclusion HO-1/BMMSC showed better immunosuppressive effects after transplantation. HO-1 could enhance the effects of BMMSC inhibiting the immune response of acute rejection in ectopic small bowel transplantation model of rats.