Alpha-lipoic acid (ALA) is a natural antioxidant that scavenges reactive oxygen species (ROS) and regenerates endogenous antioxidants. In the present study, plasma molecular markers of oxidative stress, inflammatory state, and endothelial cell injury was measured to investigate the effect of simultaneous blocking of both angiotensin (AT) II-and oxidative stress-mediated pathophysiologic pathways during the course of type II diabetic nephropathy in the clinical settings. Sixty-three diabetic subjects have carried out either of 12-month treatment course of AT-II receptor blocker (ARB) alone, ALA alone, or combination of both. Plasma malondialdehyde (MDA) level, a marker for oxidative stress, increased in ARB alone group whereas reduced to significantly lower level in ALA+ARB combination group. Plasma hs-CRP level, an inflammatory marker, decreased significantly in ARB+ALA group. Plasma thrombomodulin (TM) level, a marker of endothelial cell injury, increased in both ARB and ALA group. Twenty-four hour urinary protein excretion, as a marker of renal injury, decreased in ARB and ARB+ALA group. Finally, renal function was reserved well in ARB+ALA group in compared to others. The combined administration of ALA and ARB additively attenuated or reduced plasma markers of oxidative stress, inflammation and endothelial cell injury for one year. It suggests that the benefits in attenuating atherogenic process and vascular injury retard the progression of renal dysfunction.