Using the streptozotocin (STZ)-induced diabetic rat model, we have established a time-related curve for lipid hydroperoxides (LHP) in plasma and have correlated the period corresponding to maximal increase with histologic changes in the outer retina. Measurement of thiobarbituric acid reacting substances (TBARS) provides a convenient assessment of LHP concentration in plasma. Our results demonstrate a seven-fold elevation of TBARS at 10 days post-induction which increased to fifteen times above normal at 22 days and then fell dramatically to below baseline values at 39 days. Structural damage to the retina consisted of a reduction in cell number throughout the inner and outer nuclear layers, disorganization and loss of photoreceptor segments, and dilation of the basal region of the retinal pigment epithelium. The present observations establish a correlation between LHP concentration and retinal structure and function. Taken together with other reports in the literature showing alterations of protective enzymes and antioxidants, it appears that free radicals and lipid peroxidation are involved in the etiology of diabetic retinopathy in the STZ rat model. The TBARS assay is a simple, sensitive and inexpensive method to monitor changes in oxidative status and may prove useful in diagnosis and monitoring of patients with diabetes.