Diabetes mellitus is postulated to be associated with increased lipid peroxidation, which may contribute to vascular complications. One potential mechanism of the increased lipid peroxidation in diabetes is lipid-linked advanced glycosylation and oxidation. Aminoguanidine (AMGN), the prototype inhibitor of advanced glycosylation end product (AGE) formation, has been recently shown to prevent oxidative modification of low-density lipoprotein (LDL) in vitro at a moderate concentration. It is unknown whether AMGN may act as an antioxidant against lipid peroxidation under hyperglycemia in vivo. To investigate the in vivo effect of AMGN on lipid peroxidation in diabetes, we administered AMGN (1 g/L in drinking water) or vitamin E (400 mg/d for 5 d/wk) to streptozotocin (STZ)-induced diabetic rats for 9 weeks and measured plasma lipid hydroperoxides by ferrous oxidation with xylenol orange II (FOX method) and red blood cell (RBC) membrane malondialdehyde (MDA) and related aldehydes as thiobarbituric acid-reactive substances (TBARS). Plasma lipid hydroperoxide was higher in STZ-induced diabetic rats versus control rats (mean +/- SD, 7.53 +/- 2.03 v 5.62 +/- 0.44 micromol/L, P < .05; n = 8 to 14). RBC membrane TBARS were also higher in STZ-induced diabetic rats than in control rats (2.67 +/- 0.46 v 1.81 +/- 0.19 nmol/mL, P < .05). Plasma lipid hydroperoxide was lower in AMGN-treated (6.23 +/- 0.59 micromol/L, P < .05) and vitamin E-treated (5.29 +/- 0.27 micromol/L, P < .05) diabetic rats than in untreated diabetic rats. RBC membrane TBARS were also lower in AMGN-treated (1.93 +/- 0.12 nmol/mL, P < .05) diabetic rats than in untreated diabetic rats. There was no significant difference in plasma glucose, cholesterol, and triglyceride levels among diabetic groups. Although the mechanism(s) of action of AMGN on lipid peroxidation in vivo should be studied further, these results suggest that AMGN may have an additional beneficial effect as an antioxidant against lipid peroxidation in a prevention trial for diabetic vascular complications.