Objective To investigate the effect on expression regulation of calmodulin-dependent kinases casades (CaMK) Ⅱ on liver function after liver transplantation in rats. Methods Allogeneic orthotopic liver transplantation model was established by using the classic two-cuff method. The lentiviral expression systems of CaMKⅡγ protein and CaMKⅡγ shRNA were constructed. The lentiviral vector expressing CaMKⅡγ shRNA and the lentiviral vector expressing CaMKⅡγ protein were perfused into the rat after liver transplantation respectively, and the corresponding blank vector and normal saline were perfused into the control group at the same time. The serum levels of ALT and AST were measured at different time points of inferior vena cava blood in rats. Results The serum ALT and AST levels were debased in the after transplantation rats whose lentiviral vector expressing CaMKⅡγ shRNA (P<0.05). The serum ALT and AST levels were raised in the after transplantation rats whose lentiviral vector expressing CaMKⅡγ protein (P<0.05). There were no significant difference of serum ALT and AST levels between the blank control group and the saline group (P>0.05). Conclusion Specific blocking of CaMK Ⅱ signaling pathway can effectively reduce the serum ALT and AST levels after liver transplantation in rats, and enhanced CaMK Ⅱ signaling pathway increases the serum ALT and AST levels after liver transplantation in rats.