Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have been suggested for the category of podocytopathies. An ultrastructural observation and immunogold labeling for cytoskeleton proteins of podocytes on 11 cases each of FSGS and MCD were performed. Compared to MCD, more severe ultrastructural alterations of podocyte were identified in FSGS, which were characterized by higher frequency of mat-like condensation of microfilaments in the foot process and the detachment of the foot process from glomerular basement membrane. The labeling of alpha-actinin of podocytes in FSGS was significantly higher than MCD, which suggested an abnormal expression of cytoskeleton protein of podocyte in FSGS. The present study demonstrated a much more severe podocyte injury at the ultrastructural level in FSGS than in MCD.