Summary. We have previously showed that endothelial progenitor cells (EPCs) through uptake of hepatitis B virus (HBV) may play a critical role in mediating extrahepatic HBV diseases. However, it remains to be elucidated whether mesenchymal stem cells (MSCs) are capable of mediating HBV trans-infection into extrahepatic tissues. Methods and Results: In this study, we showed that HBV antigens, HBV DNA and the viral particles were detected in MSCs after 3 days virus challenge. Neither HBV covalently closed circular DNA nor pregenomic RNA were detected in MSCs. Intravenously transplantation of HBV-exposed MSCs into myocardial infarction mouse model resulted in incorporation of HBV into injured heart and other damaged tissues. Conclusion: These results indicate that MSCs could serve as an additional extrahepatic virus reservoir, which may play a role at least in part in mediating HBV trans-infection into the injured tissues through the process of MSCs recruitment.