Large animal cardiopulmonary bypass (CPB) models have disadvantages, such as cost, lack of methods for assessment of neurocognitive function, and difficulties with long-term recovery. As a result, rodent models have been developed. Previous rodent models have certain drawbacks, including irrelevance to human flows used clinically. We established a clinically relevant model of CPB with deep hypothermic circulatory arrest (DHCA) in the rat. Our CPB circuit has several novel features, including a small priming volume, active cooling/rewarming processes, vacuum-assisted venous drainage, peripheral cannulation without thoracotomy or sternotomy, and an accurate means of monitoring peripheral tissue oxygenation. This small animal model provides a simple experimental system that could be used in future studies that use CPB and DHCA.