Although glomerular lesions are caused by multiple mechanisms, when the lesion is severe, it frequently results in segmental or global sclerosis regardless of etiology, and contributes to progression of renal disease. Initially, glomerular mesangial cell injury was considered to be central to glomerular sclerosis. Recently, glomerular epithelial cell injury has attracted attention as the primary event of the sclerosis. Less attention has been paid to glomerular endothelial cell injury. However, the latter is acquiring increasing interest as to whether endothelial cell injury is also a crucial factor in the cause and progression of glomerular sclerosis. It has been clearly demonstrated that regeneration of impaired glomerular capillary networks plays an important role in the repair process of glomerular lesions. Glomerular endothelial cell injury exerts significant influences on the progression and repair process of glomerular disease. When the glomerular lesion is severe, angiogenesis is prevented due to endothelial cell injury, with subsequent sclerosis taking place in the impaired region. These glomerular endothelial cell injuries inevitably affect mesangial and epithelial cells and presumably modify the progression of renal disease by reciprocally interacting with them.