The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia-reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents (p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (p < 0.01) and XO (p < 0.05) activities and elevated GSH (p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group (p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.