Introduction and hypothesis: To investigate the molecular signature underlying experimental interstitial cystitis (IC) using cDNA microarray. Methods: Microarray gene expression profiles are studied inbladder epithelium of C57BL/6 mice with ovalbumin or substance P-induced experimental IC versus Escherichia coli lipopolysaccharide-induced bacterial cystitis. Results: Main findings are summarized as follows: firstly, a '75-gene' model was discovered to contain high expressions of bladder epithelium which feature in experimental IC. Secondly, glucose, lipid, nucleotide, xenobiotics, and amino acid metabolisms are involved in. Thirdly, T-cell-mediated immune and inflammatory responses are observed. Fourthly, Wnt, Tgf-beta, Mapk, and insulin growth factor receptor signaling pathways are also involved in. In addition, experimental IC leads to Ephrin- and Semaphorin-mediated axon guidance promoting parasympathetic inflammatory reflexes. Conclusions: Further characterization of human IC-induced gene expression profiles would enable the use of genome-based expression profiling for the therapeutic targets and diagnosis of IC. © The International Urogynecological Association 2009.