Aims：To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe the expression of miR-26a-5p and its target gene PTEN in the retinal of diabetic mice. Methods：Diabetic mice were induced and gavaged by fenofibrate, H&E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expreesion of miR-26a-5p, Western blotting and immunofluorescence were employed to measure the expression of phosphatase and tensin homologue(PTEN) in the retina of diabetic mice. The expression level of NF-κB (nuclear factor-κB), IL-1β (interleukin-1β) and the morphology of neural tissues were observed were examined in the retina of diabetic mice. Results：When compared with the diabetic mice, fenofibrate significantly attenuated retinal neuronal decrease and neuroretina thinning. While the level of miR-26a-5p was increased and the expression of PTEN and inflammatory factors were significantly decreased in the retina of fenofibrate threated diabetic mice(P<0.05). Conclusions: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.