Catestatin (CST), an antihypertensive peptide, is known to decrease blood pressure (BP) in Chga-/- mouse models. This prompted us to examine whether CST was similarly able to decrease BP in a spontaneously generated hypertensive and insulin resistant db/db mouse model. We used a non- invasive computerized tail-cuff method for measuring blood pressure, qPCR to determine gene expression, western blot for protein and high performance chromatography (HPLC) for determination of catecholamines after treatment with CST. Our results showed that CST was able to decrease BP in diabetic mice possibly by reducing systemic vascular resistance via the action of vasodilatory mediators, like Nitric Oxide (NO) and Atrial Natriuretic Peptide (ANP). These findings improve our understanding of CST as an antihypertensive peptide in general, as well as its role in diabetic type II mouse model