Objective: To evaluate the effect of exogenous insulin on endoplasmic reticulum stress in myocardial tissues during insulin resistance in the rabbits undergoing cardiopulmonary bypass (CPB). Methods: Forty healthy adult New Zealand white rabbits of both sexes, weighing 2.5-3.0 kg, were divided into 4 groups (n=10 each) using a random number table method: control group (group C), CPB group, CPB plus insulin group (group I) and CPB plus normal saline group (group NS). Group C received no treatment.An insulin resistance model was established in group CPB.Insulin was continuously infused (the infusion rate was adjusted according to the blood glucose) starting from establishing CPB to 1 day after operation in group I. The equal volume of normal saline was given starting from establishing CPB to 1 day after operation in group NS.Blood samples were collected from the left femoral artery, and myocardial tissues obtained before CPB (T₁) and at 15, 30 and 60 min after aortic opening (T_2-4). The level of blood glucose was determined using oxidase method, the level of glucagon was detected by the radioimmunoassay method, and the insulin resistance index was calculated.The expression of inositol-requiring protein-1α(IRE1α), XBP1 and caspase-12 was measured by Western blot.The expression of IRE1α, XBP1 and caspase-12 mRNA was measured by fluorescent quantitative real-time polymerase chain reaction.Cell apoptosis was detected by TUNEL. Results: Compared with group C, blood glucose and glucagon levels at T_2-4 and insulin resistance index at T₄ were significantly increased, and the expression of inositol-requiring protein-1α(IRE1α), XBP1 and caspase-12 protein and mRNA was up-regulated at T₄ in CPB, I and NS groups (P<0.05). Compared with group CPB, blood glucose and glucagon levels at T_2-4 and insulin resistance index at T₄ were significantly decreased, and the expression of IRE1α, XBP1 and caspase-12 protein and mRNA was down-regulated at T₄ in group I (P<0.05). Conclusion Exogenous insulin significantly improves insulin resistance in myocardial tissues, and the mechanism is related to inhibiting endoplasmic reticulum stress and reducing cell apoptosis in the rabbits undergoing CPB.