The response to retention hypothesis outlines the initial stages of atherosclerotic lesion formation. The central theme of the hypothesis is that proteoglycan mediated lipoprotein retention plays a critical step in the initiation of atherosclerosis development. Recent research using human arterial specimens, transgenic mouse models and molecular biology techniques have added to our understanding of atherosclerosis development, and provided experimental data in support of the response to retention hypothesis. In this review we summarize the recent data, in particular that which addresses mechanisms by which diabetes can accelerate atherosclerosis formation, with a focus on proteoglycan-mediated LDL retention.