Relevance. Insight into the pathophysiology of diabetic macular edema (DME) has led to novel treatments, including anti-VEGF, corticosteroid-based treatment strategies and novel therapies, such as a clusterin blood retina barrier (BRB) cytoprotection. It has been shown the protective effect of clusterin on oxidative stress-induced cell death and its emerging roles in reduction of both BRB breakdown and neural retina damage. Goal. To assess the content of serum clusterin in patients with type 2 diabetes (T2D) and diabetic macular edema depending on the type of glucose lowering therapy. Material and methods. This study was conducted in 82 patients with T2D and DME. The average age of patients was 65.25 ± 10.85 years (±SD) [25; 84], the average duration of diabetes was 14.0 ± 7.05 years (±SD) [1; 35], the average level of HbA1c was 8.40 ± 1.58% (±SD). The criteria for inclusion in the open study was voluntary informed consent, age 18 years and more, the presence of T2DM. Non-inclusion criteria were the presence of endocrine diseases, which can lead to type 2 diabetes, T1D, acute infectious diseases, cancer, decompensation of comorbid pathology, mental disorders, antipsychotics, antidepressants, neurodegenerative diseases of the central nervous system, proteinuria, damage to the optic nerve, glaucoma and mature cataracts. 43 patients received oral glucose lowering drugs (OGLD: sulfonylureas, biguanides), 39 patients received insulin therapy. All patients had instrumental ophthalmological examinations. The concentration of serum clusterin was measured by «Human Clusterin ELISA» kits. Statistical analysis was performed by one-way ANOVA analysis. Results. A study of level variability of blood clusterin in patients with DME showed its dependence from the type of glucose lowering therapy. Comparison of mean values of strum clusterin in patients with DME and T2DM revealed the following statistically significant differences: OGLD 87,08 ± 3,15 mcg/ml [95% CI 82,63 - 91,54 mcg/ml]; insulin therapy 74,79±2,98 mcg/ml [95% CІ 70,58 - 78,99 mcg/ml] (р=0,006). Apparently, clusterin is involved in the pathogenesis of DME and may have a potential in reducing of the pathogenic effect of diabetes on the neurovascular unit. The data obtained make it possible to discuss the neuroprotective role of clusterin in DME with the use of voiced oral hypoglycemic drugs, which usually prescribe for patients with mild form of T2D or for the patients with moderate severity T2D (i. e. at the initial stages of development of diabetes). Conclusion. Against the background of glucose lowering drugs in patients with type 2 diabetes and diabetic macular edema statistically significant (р=0,006) increases the content of serum clusterin compared to insulin therapy.