Cell transplantation therapy needs engraftment efficiency improvement of transplanted cells to the host tissues. Ex vivo transfection of a pro-survival gene to transplanted cells is a possible solution; however prolonged expression and/or genomic integration of the gene can be cancer promoting. To supply pro-survival protein only when it is needed， we used mRNA transfection， which exhibits transient protein expression profiles without the risk of genomic integration. Ex vivo transfection of mRNA encoding Bcl-2， a pro-survival factor， led to enhanced hepatocyte engraftment in both of normal and diseased mouse liver， effectively supporting liver function in a model of chronic hepatitis. The transplanted hepatocytes maintained their viability and function in the liver for at least one month， though Bcl-2 expression from mRNA was sustained for just a few days. Mechanism analyses suggest that Bcl-2 inhibits Kupffer cell-mediated hepatocyte clearance， which occurs within 2 days after transplantation. Within 2 days， hepatocytes migrated to the liver parenchyma， presumably a suitable place for the hepatocytes to survive without Bcl-2 expression. Thus， the duration of Bcl-2 expression from mRNA was sufficient to achieve prolonged engraftment. Ex vivo mRNA transfection allows supply of pro-survival factors to transplanted cells with minimal safety concerns accompanying prolonged expression， providing an effective platform to improve engraftment efficiency in cell transplantation therapy.