In order to elucidate a participation of the mesangiolysis in the formation of diabetic nodular lesions, 355 kidney specimens obtained from 327 patients with primary diabetes mellitus were studied. Mesangiolyses begun by focal and segmental disintegration of the pivotal structure of the mesangium ("torn off phase"), resulting in cystic or aneurysmal dilatation of the involved tuft, were found in 56 specimens (16%). The dilated tufts were filled with lysed mesangial matrix, which showed a reticular or fibrillar arrangement ("structureless phase"), being followed by a concentrical re-arrangement ("reconstructive phase") and by the ultimate formation of diabetic nodules. The mesangiolysis of various phases was frequently found concomitant with severe diabetic arteriolosclerosis and, in the reconstructive phase, the lysed mesangial matrix near the recanalized capillary along the inner aspect of glomerular basement membrane was observed to be rearranged in a layered structure. These results suggest the hypothesis that: 1) the mesangiolysis is the initial lesion occurring in glomeruli in the process of diabetic nodule formation, and disturbed blood flow into glomeruli, caused by diabetic arteriolosclerosis, may be implicated in the development of the mesangiolysis; and 2) concentric compression of the lysed mesangial matrix by recanalized capillaries forms layered structures and ultimate completed diabetic nodules.