Iron overload is known to affect erythrocyte membrane properties and erythrocyte shape. We hypothesized that iron overload which directly affects the erythrocyte morphology may also interfere with erythrocyte deformability (ED). Exenatide, a glucagon like peptide -1 (GLP-1) analogue used in the treatment of diabetes, is known to have beneficial pleiotropic effects on endothelial function and blood flow which are different from its glucose-lowering effects. In our study we aimed to test the effect of iron overload on ED in a rat model (1) and to evaluate the effect of exenatide on ED in the same model (2). For this purpose, the animals were randomly divided into three groups, each containing 6 rats. Rats in the control group (Group C) were given intraperitoneal injections of saline as placebo. The second group (Group Fe) was given intraperitoneal iron dextran (60 mg/kg/day) five days a week for 4 weeks to develop iron overload. The third group (Group Fe + E) received subcutaneous injections of 10 mcg exenatide (Byetta (R) Lilly Pharma) in two divided doses for 4 weeks in addition to iron dextran. We observed that ED index was significantly higher in Group Fe when compared to Group C and Group Fe+E (p <0.0001, p <0.0001). Administration of exenatide to the iron-loaded rats (Group Fe +E) led to a significant decrease in the deformability index (p < 0.017) when compared to Group Fe. Our study shows a decrease in ED with iron and beneficial effect of exenatide on ED in the iron-overloaded rat model (Fig. 1, Ref. 24). Text in PDF www.elis.sk.