Purpose-Interstitial cystitis (IC) is a painful bladder syndrome associated with urinary frequency and urgency. Elusive etiology of IC makes its diagnosis only possible by exclusion in many cases. In the present study, we used proteomics for identifying disease-associated proteins in rat model of chronic bladder irritation.Materials & Methods-Chronic irritation of rat bladder was caused by a brief (90 secs) intravesical instillation of 0.2ml of 0.4N HCl. Whole bladders were collected at different time points after treatment, snap frozen and nuclear and cytosolic protein extracts were obtained. Samples were resolved in standard 2D-gels stained with an improved Coomasie Stain or by Differential Gel Electrophoresis (DIGE). Differentially expressed spots were excised and identified by MALDI-TOF MS/MS. Histological and Western blot analysis were also performed.Results-Bladder morphology and histologic appearance of bladder sections following HCl treatment reflected hemorrhage, edema, epithelial denudation, detrusor mastocytosis and eosinophilia. Proteomic analysis of irritated rat bladder revealed marked overexpression of four nuclear proteins and marked underexpression of one nuclear protein compared to normal rat bladders. Among these proteins, inflammation-associated Calgranulin A (over) and smooth muscle protein-22/transgelin (under) showed opposed expression patterns following bladder irritation.Conclusions-Presence of mast cells and eosinophils and overexpression of calgranulin A confirm the inflammatory component of HCl-irritated bladder. Altered expression of nuclear proteins is of particular interest because of their possible role as a prognostic marker in inflammatory bladder disorders. However, more studies are needed before clinical application of these findings can be established.