Diabetes is one of the risk factors to human health, which progressively leads to renal complications known as diabetic nephropathy. Many previous studies illustrated biochemical and morphological abnormalities in various animal models of diabetic nephropathy, which may be attributed to altered action of adenosine, an endogenous purine nucleoside released from various tissues and organs. Adenosine is a potent autocrine anti-inflammatory and immunosuppressive molecule that is released from cells into the extracellular space at sites of inflammation and tissue injury. This review will give a general overview of the adenosine receptors and focuses on their role in diabetes nephropathy. The insight into the signaling pathway through adenosine receptors could be helpful in developing novel therapeutic tools to regulate the pathophysiological conditions that arise progressively in diabetes.