Objective To evaluate the effect of exogenous insulin on inositol-requiring protein 1α (IRE1α)-X-box-binding protein 1 (XBP1) signaling pathways in pancreatic tissues during cardiopulmonary bypass (CPB)-caused insulin resistance in rabbits.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),group CPB,insulin group (group I),and normal saline control group (group NS).CPB was established in group CPB.Insulin was intravenously infused in a dose of 1.2 ml/h from establishing CPB to 1 day after operation,and the infusion rate of insulin was regulated according to the blood glucose (maintaining at 7.2-8.3 mmol/L) in group I.CPB was established,and normal saline was intravenously infused from the beginning of operation to 1 day after operation in group NS.Before CPB (T1) and at 15,30 and 60 min after aortic opening (T2-4),blood samples were collected from the left femoral artery,the plasma was separated,the blood glucose level was detected by oxidase method,the level of glucagon was detected by the radioimmunoassay method,and the insulin resistance index was calculated.Animals were sacrificed at T4,and pancreatic tissues were obtained for determination of the expression of IRE1α,XBP1,c-Jun N-terminal kinase (JNK) and caspase-12 protein and mRNA (by Western blot or fluorescent quantitative real-time polymerase chain reaction) and for examination of the pathological changes (by haematoxylin and eosin staining).Results Compared with group C,blood glucose and glucagon concentrations and insulin resistance index were significantly increased at T2-4,and the expression of IRE1α,XBP1,JNK and caspase-12 was up-regulated at T4 in CPB,I and NS groups (P＜0.05).Compared with group CPB or group NS,blood glucose and glucagon concentrations and insulin resistance index were significantly decreased at T2-4,the expression of IRE1α,XBP1,JNK and caspase-12 was down-regulated at T4 (P＜0.05),and the pathological changes of pancreatic tissues were significantly attenuated in group I.There was no significant difference in the parameters mentioned above between group CPB and group NS (P＞0.05).Conclusion The mechanism by which exogenous insulin reduces CPB-caused insulin resistance may be related to inhibiting IRE1α-XBP1 signaling pathways in pancreatic tissues of rabbits.