Diabetes mellitus (DM) is a metabolic disease characterized by numerous serious complications. One of the most common is diabetic nephropathy (DN), a chronic deterioration of renal function in patients with DM, leading to a loss of serum albumin in the urine, a decrease in glomerular filtration, and consequent renal failure. Long-chain polyunsaturated fatty acids (PUFA; polyunsaturated fatty acids) have been studied in recent decades for their nutritional value and potential health benefits when absorbed into the body. Numerous pathological conditions in tissues have been associated with a change in the proportion of PUFA in tissues. The aim of this study was to investigate the effects of experimental type 1 diabetes (DM1, diabetes mellitus type 1) and to determine the potentially protective/harmful effect of the different ratio of dietary n-6/n-3 PUFA on the fatty acid composition of phospholipids in renal tissue and the pathological changes caused by DM1. Twenty-five male Wistar rats were divided into 4 groups and fed different ratios of n- 6/n-3 PUFA in the meal. The control group (eng. control C) and the diabetic group (STZ) were fed diets with an n-6/n-3 ratio of ≈ 7, the STZ+N6 group was fed diets with an n-6/n-3 ratio of ≈ 60, and the STZ+DHA group was fed diets with an n-6/n-3 ratio of ≈ 1, which consisted of 16% eicosapentaenoic acid (EPA) and 19% docosahexaenoic acid (DHA). Streptozotocin or phosphate buffer was administered intraperitoneally to the animals. Thirty days after DM1 induction, the rats were sacrificed. Kidney tissue and blood samples were collected to analyze the fatty acid composition of phospholipids and to examine pathohistological changes, ectopic lipid accumulation, and expression of vascular endothelial growth factor (VEGF), nuclear factor kappa B (NF-kB), and chromatin organizing/global transcriptional regulator protein (SATB1 English special AT-rich sequence-binding protein-1). Pathological changes were examined by transmission electron microscopy (TEM) after VEGF staining. As a result of this experiment, DM1 and the different levels of n-6/n-3 PUFA in the diet led to significant changes in the fatty acid composition of phospholipids. DM1 consequently led to extensive vacuolization of distal tubule cells, but this was significantly lower in the STZ+DHA group, in which the highest renal Nf- KB expression was also recorded. The pronounced accumulation of neutral lipids was observed in the cells of proximal tubules of all diabetic animals, but the accumulation was significantly higher in the STZ+N6 group. To our knowledge, there is no study that has investigated the effects of the n6/n3 PUFA ratio in experimentally induced DM1 on the expression of VEGF, NF-kB, and SATB1. In all diabetic animals we found disturbance of VEGF- transporting vesicular proximal tubules cell system, which was substantially worsened in the groups STZ+N6 and STZ+DHA. We also determined and analyzed the immunoreactivity of a new marker of damage in the distal tubuli and glomeruli- SATB-1, due to its key role in the pathophysiology of diabetic nephropathy. Thus, very strong immunofluorescence SATB1 was found in distal tubuli of diabetic rats, and an increased percentage of SATB1-immunoreactive distal tubular cells were found in the STZ+DHA and STZ+N6 group. Ultrastructural analysis confirmed that VEGF uses an endocytosis system for its transport, addition of PUFA did not help in the restoration of vesicular VEGF transport that was damaged in DM1. The results have shown that in the early stages of DN there is extensive damage and vacuolization of the cells of the distal tubules, which can be attenuated by EPA/DHA supplementation. These data focus on the distal tubules as an important segment in the early treatment and prevention of renal injury. Considering the paucity of studies, it is necessary to further investigate the pathophysiological changes and mechanisms of distal tubule damage. We can conclude that the fatty acid composition resulting from dietary manipulation may strongly influence the outcomes of DN. An appropriate ratio of n-3/n-6-PUFA in the diet has a beneficial effect on reducing distal tubule damage. Further studies are needed to confirm or refute the above results and to further clarify the effects of different n-3/n-6-PUFA ratios on distal tubule damage.