Objective: To characterize cell membrane mechanical fluctuations of red blood cells (RBCs) in patients with diabetic retinopathy. Methods: Point dark-field microscopy-based recordings of these local displacements of the cell membrane in human erythrocytes were compared between patients with severe proliferative diabetic retinopathy and healthy controls. The study was performed on discoid RBCs. Results: The average of the maximal displacement amplitude in the diabetic patients was 13.9% ± 1.7% (236 ± 29 rim) compared with 18.7% ± 1.75% (318 ± 30 nm) for the controls (P<.001). The decrease of the RBCs' average displacement amplitude was not correlated with the variation in negative curvature of the central area of discoid cells. Conclusions: Microdisplacements of the cell membrane, which reflect the bending deformability of the RBCs, are directly connected with its efficiency in passing through capillaries narrower than its own diameter. These microdisplacements were significantly reduced in patients with severe diabetic retinopathy because of an increase in viscoelasticity of the cell membrane Such reduced cell membrane microdisplacements, which reflect lower bending deformability of the RBC, reduce the ability of the cell to enter and pass through small capillaries, increasing tissue ischemia and consequently contributing to the development of diabetic retinopathy.