Objective To determine whether lidocaine can improve the cerebral protection provided by retrograde cerebral perfusion. Methods Sixteen mongrel dogs were placed on cardiopulmonary bypass and cooled to 20℃. Retrograde cerebral perfusion was then carried out for 120 minutes, with the external jugular venous pressure kept at 3.33 kPa. Cardiopulmonary bypass was resumed, and the animals were rewarmed to 36℃. The animals were divided into two groups. In the lidocaine group (n=8), lidocaine was administrated continuously throughout the experiment. In the control group (n=8), normal saline was given at the same rate. Results In both groups, cerebral tissue creatine phosphate and adenosine triphosphate concentrations and energy charge increased by the end of hypothermic cardiopulmonary bypass, decreased continuously during retrograde cerebral perfusion, and recovered gradually after resuming cardiopulmonary bypass. Nevertheless, they recovered to significantly higher levels in the lidocaine group than in the control group (creatine phosphate: 2.44±0.53 versus 1.61±0.49 μmol/g wet weight, P=0.006; adenosine triphosphate: 0.71±0.18 versus 0.50±0.17 μmol/g wet weight, P=0.029; energy charge: 0.59±0.10 versus 0.48±0.09, P=0.044) by the end of the experiment. There was no significant difference between the two groups in the cerebral tissue water content (control group: 77.6%±1.9%; lidocaine group: 77.6%±1.3%).Conclusion Continuous lidocaine infusion accelerates the recovery of cerebral tissue high energy phosphate contents after resuming cardiopulmonary bypass, but it has no effect on the formation of cerebral edema after retrograde cerebral perfusion.