It has been shown that adiponectin (APN) and plasminogen activator inhibitor type 1 (PAI-1) are inversely involved in the regulation of atherosclerosis formation. However, the clinical impact of APN and PAI-1 in type 2 diabetes mellitus (T2DM) with macrovascular diseases (MVD) has not been investigated. In the present study, we found that plasma APN levels were significantly lower in T2DM patients than healthy donors, with a further decrease in T2DM patients with MVD. In contrast, plasma PAI-1 levels were significantly higher in T2DM patients than healthy donors, with a further increase in T2DM patients with MVD. We observed that plasma APN levels negatively correlated to values of BMI, FBG, FINS, TG, and PAI-1 in T2DM patients. In patients with MVD, plasma APN levels were negatively associated with values of BMI, SBP, FBG, FINS, TG, and PAI-1. By multiple stepwise regression analysis, we found that values of BMI, FCP, PAI-1, and FBG independently related to plasma levels of APN in T2DM patients with MVD. Taken together, our results indicate that APN might be a promising biomarker in patients with T2DM, especially in those with MVD.