In order to investigate whether short- or long-term glycemic fluctuations could induce oxidative stress and chronic inflammation, we evaluated the relationships between glycemic variability, oxidative stress markers, and high-sensitivity C-reactive protein (hs-CRP). We enrolled 34 patients with type 2 diabetes. As a measure of short-term glycemic variability, mean amplitude of glycemic excursions (MAGE) was computed from continuous glucose monitoring system data. For determining long-term glycemic variability, we calculated the standard deviation (SD) of hemoglobin A1c (HbA1c) levels measured over a 2-year period. Levels of oxidative stress markers: 8-iso-prostaglandin F2α (8-iso-PGF2α), thiobarbituric acid-reactive substance (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), and hs-CRP were measured. MAGE was significantly correlated with the SD of HbA1c levels (r = 0.73, p < 0.001) but not with HbA1c level. The levels of hs-CRP, TBARS, 8-OHdG, and 8-iso-PGF2α were significantly correlated with MAGE (r = 0.54, p = 0.001; r = 0.82, p < 0.001; r = 0.70, p < 0.001; r = 0.60, p < 0.001) and the SD of HbA1c levels (r = 0.53, p = 0.001; r = 0.73, p < 0.001; r = 0.69, p < 0.001; r = 0.43, p = 0.01) but not with HbA1c level. Relationships between 8-iso-PGF2α and MAGE or the SD of HbA1c levels remained significant after adjusting for other markers of diabetic control (R(2) = 0.684, R(2) = 0.595, p < 0.001, respectively). Both acute and chronic blood glucose variability can induce oxidative stress and chronic inflammation.