AIM: To observe the effect of RBC preservation solution with sodium pyruvate on the morphology, structure and function of RBC stored in vitro in type 2 diabetes rats.?METHODS: Thirty SPF male SD rats,were randomly divided into 3 groups (n=10): non-T2DM conventional RBC preservation solution (group A), T2DM conventional RBC preservation solution (group B) and T2DM sodium pyruvate RBC preservation solution (group C).?The leukoreduced RBC from the tail vein and stored for 0 d (T0), 7 d (T1), 14 d (T2), 21 d (T3) and 28 d (T4) to detect the morphology, structure and the contents of 2,3-DPG, reactive oxygen species (ROS), malondialdehyde (MDA) and lactic acid (LA) of RBC in group A, B and C. The RBC stored for 14 days in vitro were labeled with PKH26, and its survival rate were tested in vivo at 1, 4, 10 and 16 hours after intravenous infusion. RESULTS: At T0, the RBC morphology of group A was intact, which was better than that of group B and group C. With the extension of storage time, the morphology of RBC in each group gradually transformed into a spindle-spherical shape. Compared with group A, the incidence of acanthocytes in group B and group C was higher, and the incidence of acanthocytes in group C was lower than that in group B. Compared with group A, the content of 2,3-DPG in group B and group C decreased, while ROS and MDA increased at different time points (P<0.05). The content of