Diabetic microangiopathy has become a heavy social burden worldwide, but at present it is still difficult to predict and diagnose this ailment at an early stage. Various proteomics approaches have been applied to the pathophysiological study of diabetic microangiopathy. Conventional proteomics methods, including gel-based methods, exhibit limited sensitivity and robustness and have typically been used in high- or middle-abundance biomarker discovery. Clinical samples from patients with diabetic microangiopathy, such as biopsy samples, are minute in size. Therefore sample preparation, quantitative labelling and mass spectrometry technologies need to be optimized for low-abundance protein detection, multiple-sample processing and precision quantitation. In this review, we briefly introduce the recent technological developments in proteomics methods and summarize current proteomics-based, translational research on diabetic microangiopathy. Recent technological developments in proteomics tools may shed new light on the pathogenesis of diabetic microangiopathy and biomarkers and therapeutic targets related to this condition.