Here, we provide the first evidence that NFAT5 and AQP1 are involved in the hypertonicity‐related induction of arterial stiffening, since NFAT5 and AQP1 were increased in the aortas of diabetic Ins2+/Akita mice exposed to high glucose‐induced hyperosmolar stress, independent of the presence of hypercholesterolaemia. Here, NFAT5 is linked to Hypercholesterolemia.