A method for diagnosing, or differentially diagnosing, interstitial cystitis (IC) involves detecting or measuring increased expression of a biomarker Endothelin 1 (ET-1) in a biological sample from a mammalian subject, particularly in the urine or urothelial tissue. An increased level of expression of ET-1 above the level of expression in the same sample of a healthy mammalian subject is an indication of a diagnosis of IC. Such diagnosis may further involve identify other clinical symptoms of IC. Additionally the method may use additional biomarkers, such as Hb-EFG, EGF, APF, IL-8, IL-6, and cGMP. Assay methods and diagnostic reagents and kits for such diagnosis are provided. Methods and compositions for treating IC by reducing the action, production or synthesis of ET-1 in the urine or urothelium and/or inhibiting its binding to its ETA and/or ETB receptors are also provided.