Chronic kidney failure is the leading cause of morbidity and mortality in individuals with diabetes mellitus (DM). To date, the underlying cause for this remains poorly defined and this has prevented the development of drugs to prevent/slow its development. This study investigates longitudinal changes in morphology, fibrosis and expression of extracellular matrix (ECM) proteins in kidneys of rats with type 1 DM. Type 1 DM was induced in male Wistar rats (n =16) using a single dose of streptozotocin (STZ; 60 mg/kg body weight, ip) dissolved in citrate buffer. Age-matched control rats (=16) received an equivalent volume of citrate buffer alone. Eight and sixteen weeks after STZ injection animals were euthanized and perfused with phosphate buffered saline. Kidneys were then harvested and processed histologically to examine morphological changes using conventional staining and quantitative assessment of fibrosis, respectively. Immunohistochemical studies were also conducted to assess apoptotic markers governed by Caspase-3. Molecular biology techniques were also employed to examine gene expressions of proteins encoding ECM components, TGFβ-1 and hypertrophy biomarkers ANP and BNP along with ELIZA to quantify the level of total and active TGFβ-1. The project had the relevant Home Office Ethical Clearance. After 8 and 16 weeks of DM, body weights were reduced (ANOVA, Bonferroni corrected t-tests, p<0.05, Mean±SEM) 270±5.78 vs. 343±9.99 and 221±13.02 vs. 378±10.63 compared to controls. Blood glucose, kidney weights, kidney weight to body weight ratio, were higher in DM rats compared to controls. Typically, blood glucose levels (mg/dl) and kidney weight/body weight ratio (g/100 g body weight) after 2 and 4 months DM were 443±12.2 and 0.15±0.02 and 446±18.8 and 0.20±0.03 compared to 98±3.79 and 0.94±0.01 and 97±3.04 and 0.82±0.01 (n=8), in controls. DM induced structural changes in the kidneys including dilated tubules and severe disorganization of the glomeruli. Electron microscopy study revealed significant increase (p<0.05) in glomerular basement membrane, meanwhile morphometric analysis indicated (p<0.05) increments in fibrous tissue proliferation and apoptosis compared to controls. This was accompanied by (p<0.05) increases in expressions of genes encoding a variety of extracellular matrix proteins including collagen 1α, collagen 3α, fibronectin, elastin, MMP9, TIMP4, CTGF, integrin α5, vimentin TGFβ-1, and hypertrophy biomarkers ANP and BNP compared to controls. Additionally, TGFβ-1 total and active levels increased significantly (p<0.05) in DM compared to age-matched controls. These alterations were more pronounced (p<0.05) after 4 months compared to 2 months DM rats. The results reveal that type 1 DM is detrimental to kidney structure and function leading to Diabetic Nephropathy (DN), symptomatic of TGFβ-1 activity.