The aim of this study was to investigate pathophysiological alterations and oxidative stress in various stages of streptozotocin (STZ)-induced diabetes mellitus (DM) in rats. Male Sprague-Dawley rats (120) were randomized into DM and control groups. Body mass, plasma glucose, glycated hemoglobin (HbA1c), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, as well as aldose reductase (AR) activities, in brain tissue and serum were determined. Electron microscopy was used to observe neuron and vessel changes in the brain. In STZ-treated rats, blood glucose, low density lipoproteins, triglycerides and total cholesterol levels increased 1.43-3.0-fold and high density lipoprotein, HbA1c and insulin sensitivity index increased 1.1-1.23-fold compared with control. At week 16 following treatment, DM rat serum H2O2 concentration was increased, indicating oxidative stress and mRNA levels of GPx and SOD were 2-fold higher than the control. Protein GPx and SOD levels were reduced (P<0.01). DM rats were identified to exhibit early irregular glomerular capillary basement membrane thickening and vacuolization in the mitochondria and epithelial cells. Neuron cells and blood vessels in the DM rat brains became increasingly abnormal over time with altered Golgi bodies, mitochondria and endoplasmic reticulum cisterns, concurrent with SOD inactivation and AR protein accumulation. Disease progression in rats with STZ-induced DM included brain pathologies with vascular and neuron cell abnormalities, associated with the reduction of SOD, CAT and GPx activities and also AR accumulation.