Knowledge regarding tissue reactions within coil-packed aneurysms is poor. The purpose of this study was to analyze histological changes in a chronic experimental bifurcation aneurysm model that might explain the protective effect of Guglielmi detachable coils. The aneurysms were produced by means of a venous graft pouch at a surgically created bifurcation of the carotid artery in the neck of rabbits. After 3 weeks, embolization with Guglielmi detachable coils was performed in the treatment group but not in the control group (seven rabbits each). At the time of embolization, six of seven treated aneurysms were completely occluded according to radiological criteria. Twelve weeks later, all aneurysms were explanted after final angiography. Histological examinations were performed with coils in situ. Six of seven embolized aneurysms demonstrated complete occlusion in final angiography. But gross pathology revealed that all specimens had differently sized open cavities between the coils. In only two cases, these spaces were very small and the aneurysmal sacs were filled with coils and tissue by more than 90%. Light microscopy demonstrated intraluminal granulation tissue and strong chronic inflammatory wall thickening with numerous foreign body cells at the interface between coils and tissue. Coils were partially incorporated into the aneurysmal wall, sometimes close to the surface and occasionally even outside the wall within the surrounding tissue. The protective effect of Guglielmi detachable coil treatment in our chronic experimental bifurcation aneurysms results from formation of intraluminal granulation tissue and wall thickening attributable to chronic inflammation.