The aim of this study was examine the effects of high starch (HS) vs. high fat (HF) feeding on blood glycated hemoglobin (GHbA(1c)) level, thiobarbituric acid-reactive species (TBA-RS) concentration and delta-aminolevulinate dehydratase (delta-ALA-D) activity in mice. The GHbA(1c) level was significantly higher in mice fed the HF diet compared with those fed the HS diet. Hepatic, renal, and cerebral TBA-RS concentrations in mice fed the HF diet were significantly greater than in mice fed the HS diet. In addition, positive correlations were found between the GHbA(1c) and TBA-RS levels for hepatic (P < 0.05; r = 0.46), renal (P < 0.003; r = 0.65), and cerebral (P < 0.001; r = 0.69) tissues. The delta-ALA-D hepatic, renal and cerebral activities of mice fed the HF diet were significantly lower than those of mice fed the HS diet. Furthermore, a negative correlation was found between the GHbA(1c) level and delta-ALA-D activity in hepatic (P < 0.001; r = -0.77), renal (P < 0.007; r = -0.60), and cerebral (P < 0.007; r = -0.60) tissues. The results of this study indicate that consumption of a high fat diet promotes oxidative stress related to hyperglycemia, which in turn can stimulate glycation of proteins leading to delta-ALA-D inhibition in mice.