Chronic kidney disease is associated with vasculitis and is also an independent risk factor for peripheral vascular and coronary artery disease in Diabetic patients. Despite optimal management, a significant number of patients progress towards end-stage renal disease (ESRD), a suggestion that the disease mechanism is far from clear. A reduction in hydrogen sulfide (H2S) has been suggested to play a vital role in diabetic vascular complications including diabetic nephropathy (DN). This mini review highlights the recent findings on the role of hydrogen sulfide (H2S) in mitigating abnormal extracellular matrix metabolism in DN. A discussion on the development of the newer slow releasing H2S compounds and its therapeutic potential is also included.