Introduction and hypothesis: The aim of the study was to investigate the molecular signatures underlying bladder pain syndrome/interstitial cystitis (BPS/IC) using cDNA microarray. Methods: Microarray gene expression profiles are studied in a matched case-control studies by using a system of conditional regression modeling. Results: Main findings are summarized as follows: Firstly, a "139-gene" model was discovered to contain high expressions of bladder epithelium, which feature in BPS/IC. Secondly, complex metabolic reactions, including carbohydrate, lipid, cofactors, vitamins, xenobiotics, nucleotide, and amino acid metabolisms, are found to have a strong relationship with bladder smooth muscle contraction through IC status. Thirdly, we have found the transcriptional regulations of IC-induced bladder smooth muscle contraction status, including the level of contractile force, tissue homeostasis, energy homeostasis, and the development of nervous system. In addition, our study suggested the mast-cell activation mediated by the high-affinity receptor of Fc episilon RI triggering allergic inflammation through IC status. Such genetic changes, jointly termed "bladder remodeling" can constitute an important long-term consequence of phosphate-buffered saline (PBS)/IC. Conclusions: The success of this innovation has supported the use of microarray-based expression profiling as a single standardized platform for diagnosis of PBS/IC and offer drug discovery. © The International Urogynecological Association 2009.