Müller cells, as the special radial glial cells in the retina, span the entire retina, contact with neurons, microvessels and processes in the retina and play a significant role in protecting retinal structure and function.Diabetic retinopathy (DR) is a major ocular complication of diabetic patients.In the progression of DR, diabetic macular edema (DME) is the main cause of vision loss.During the occurrence of DME, the morphological and structural changes of Müller cells including severer swelling and vacuolation of cell bodies, increased apoptosis, and abnormal secretion of cytokines, etc.damage the blood-retinal barrier (BRB), increase the permeability of BRB and accelerate the exudation of subretinal fluid.In addition, Müller cells can disrupt the regulation of K⁺ and water transportation, obstruct the fluid absorption in the subretinal space and promote the formation of DME.However, in the early stage of DR, neurotrophic factors secreted by Müller cells can protect the retina by alleviating retinal edema and protecting optic ganglion cells, suggesting that Müller cells can be used as targets for DME treatment.Therefore, new strategies can be provided by fully exploring the role and mechanism of Müller cells in the formation of DME.In this paper, the mechanism of Müller cells in DME and its protective role in the progression of DME were reviewed.