To investigate the protective effect of Neuregulin-1 (NRG-1) on nerve injury in early diabetic retinopathy rats. Methods: Total 30 SD rats were randomly divided into groups control (CONT), diabetes mellitus (DM), and NRG-1 treatment, with 10 rats in each group. Rats in the last two groups were administered Streptozotocin (STZ) by a single intraperitoneal injection to create the DM model. After successful establishment of the model, the NRG-1 treatment group received intravitreal injections of recombinant NRG-1, and the CONT and DM groups were given equal volume injections of normal saline. Four weeks later, the density of retinal ganglion cells (RGC) were detected by HE staining, expression of glial fibrillary acidic protein (GFAP) and microtubule associated protein-2 (MAP-2) were detected by immunofluorescence, and relative expression levels of retinal GFAP and MAP-2 were detected by Western blot. Results: Compared with the CONT group, the DM group showed significantly increased GFAP expression and significantly decreased MAP-2 expression and RGC density (all P<0.01). Compared with the DM group, the NRG-1 group displayed significantly decreased GFAP expression and significantly increased MAP-2 expression and RGC density (all P<0.01). Conclusion: NRG-1 can increase the expression of retinal MAP-2 and restore the density of RGC by inhibiting the activation of glial cells. NRG-1 may have protective effects on the neuropathy of early diabetic retinopathy rats.