Despite the advances in molecular cell biology, identification of a therapeutic target in a given disease still poses a significant challenge. Here we report a strategy for identification of the therapeutic target in abdominal aortic aneurysm (AAA). We screened for various signaling molecules in human AAA samples and identified c-Jun N-terminal kinase (JNK) as a prominently activated molecule. The JNK pathway-oriented transcriptome analyses revealed that activation of JNK leads to enhancement of the activity of matrix metalloproteinases and, concurrently, suppression of the extracellular matrix biosynthesis, suggesting that JNK may represent a novel therapeutic target in AAA.