Aim: This study aimed to evaluate the effects of sorafenib on macroglial and microglial activation in the retina under diabetic conditions, using a streptozoto cin- induced model of diabetic retinopathy. Special emphasis was placed on examining early and chronic phases of gliosis, assessing molecular markers of glial activation, and determining whether sorafenib can attenuate glial remodelling and neuroinflammation in the diabetic retina. Materials and Methods: Sixty male Wistar rats were divided into three groups: untreated diabetic controls, insulin-treated, and insulin + sorafenib-treated. Diabetic retinopathy was induced via intraperitoneal injection of streptozotocin (50 mg/kg). Retinal samples were collected at 7, 14, 28 days, and 3 months post-induction. Histological analysis (H&E staining), immunohistochemistry (GFAP, S100), and Western blotting (GFAP, Iba-1) were used to assess glial activation. Statistical analysis was conducted using ANOVA with significance set at p < 0.05. Results: Untreated diabetic rats exhibited severe retinal oedema, neurodegeneration, and increased GFAP, S100, and Iba-1 expression, indicating pronounced macroglial and microglial activation. Sorafenib co-treatment significantly reduced the expression of glial markers and preserved retinal structure, with near-complete suppression of gliosis and no evidence of glial-mesenchymal transition. These effects were more pronounced than those of insulin monotherapy. Conclusions: Sorafenib attenuates retinal glial activation and neuroinflammatory changes in experimental diabetic retinopathy, suggesting its potential as a neuroprotective and antifibrotic agent. Targeted kinase inhibition may represent a promising adjunct strategy in early-stage disease management