To evaluate how creatine influences erythrocyte deformability, we determined its effect on erythrocyte filterability in 9 subjects with insulin dependent diabetes (IDDM) without complications, 14 diabetics with uremia and 10 non‐diabetic controls. The short‐term incubation (15 min at 37
{}^{\circ}
C) of diabetic erythrocytes with 3 mM creatine improved cell filterability (assessed according to the Reid method) from IDDM subjects without complications by 28.4% and that from diabetics with uremia by 18.9%. No rheological effect of creatine was found in erythrocytes from non‐diabetic controls. However, a significant protective effect against erythrocyte filterability impairment induced by treatment of red blood cells from non‐diabetic controls with hydrogen peroxide was observed with 3 mM
(p < 0.04)
and 5 mM
(p < 0.01)
creatine, respectively. Measurement of the thiobarbituric acid (TBA) reactivity was used to assess hydrogen peroxide induced formation of malondialdehyde (MDA). We found that creatine inhibits hydrogen peroxide‐induced erythrocyte MDA‐formation in a dose dependent manner by 20.4%, 22.3% and 41.4% for 1, 3 and 5 mM creatine, respectively. These results suggest that creatine by its ability to inhibit erythrocyte lipid peroxidation may contribute to the maintenance of normal cell deformability.