Background: Diabetes is a risk factor for perioperative complications after cardiac surgery. We studied its effects on mesenteric endothelial function in a cardiopulmonary bypass (CPB) model. Methods: Forty Wistar rats were divided into four groups: sham (D-CPB-), cardiopulmonary bypass (D-CPB+), diabetic (D+CPB-) and diabetic that have undergone CPB (D+CPB+). Two samples of mesenteric artery were used for nitric oxide synthase (NOS) Western blot analysis, and two others for assessing contractile response and endothelium relaxations. Nitrite products and tumour necrosis factor-alpha (TNF-α) were assessed as markers of inflammatory response. Results: We observed an enhanced contractile response to the α-adrenergic agonist associated with impairment of mesenteric vasorelaxation in D+CPB+ rats. Western immunoblot analysis of D+CPB+ highlighted an additive effect of hyper-expression of inducible NOS. A significantly increased inflammatory response was observed after CPB in diabetic animals. Conclusions: This work confirms the potential deleterious impact of diabetes on the mesenteric endothelium during CPB in cardiac surgery.