Cerebral aneurysm is a common disease with a high prevalence and can cause a catastrophic subarachnoid hemorrhage. To elucidate the molecular mechanism of the formation and progression of cerebral aneurysms, gene expression profiling was performed in experimentally induced rat cerebral aneurysms. The intima and media of cerebral arterial walls in rats with or without aneurysm induction were dissected respectively by a laser-microdissection technique. Changes in gene expression in the intima and media of aneurysmal walls were analyzed using Agilent Rat Oligo Microarrays, followed by a specific pathway analysis using GeneSpring software. Of the 41,012 genes examined, 633 were differentially expressed between a normal cerebral artery and a cerebral aneurysm in the intima, with 395 showing increased expression and 238 showing decreased expression. In the media, 1344 were differentially expressed, with 928 showing increased expression and 416 showing decreased expression. Specific pathway analysis revealed that increased gene expression was associated with proteinase, reactive oxygen species, growth factor, chemokine, complement, adhesion molecule and apoptosis in both the intima and the media of aneurysmal walls. Some genes showed an opposite expression pattern between the intima and the media indicating a different role between endothelial cells and vascular smooth muscle cells in cerebral aneurysm formation and progression. These data suggest that cerebral aneurysmal formation and progression are closely related to vascular inflammation, degeneration of extracellular matrix and apoptosis.