Ischemia/reperfusion (I/R) injury is considered to be a contributing factor in liver injury following major hepatic resection or liver transplantation. Bone marrow mesenchymal stem cells (BM‑MSCs) have the potential to protect against liver I/R injury; however, the precise mechanisms have not been completely elucidated. Autophagy serves an important role in protecting against various injuries, including I/R injury. The present study aimed to determine the role of autophagy and its potential regulatory mechanism in BM‑MSC‑mediated protection against liver I/R injury in rats. The results demonstrated that BM‑MSCs mitigated I/R injury and enhanced autophagy in vivo. In addition, inhibition of autophagy by 3‑methyladenine reversed the positive effects of BM‑MSCs. Furthermore, heme oxygenase‑1 (HO‑1) expression was promoted by BM‑MSCs. Using zinc protoporphyrin IX to inhibit HO‑1 demonstrated that HO‑1 was important for the promotion of autophagy. In conclusion, the present study revealed that BM‑MSCs protected against liver I/R injury via the promotion of HO‑1‑mediated autophagy.