This study was conducted to set up a common mechanism for varying phases of focal segmental glomerulosclerosis(FSGS) by comparing the morphological differences between human FSGS and changes in 5/6 renal ablation animal model, which has been accepted as experimental prototype for hyperfiltration theory as pathogenesis of FSGS. Both the human and the experimental rats showed very similar changes such as segmental glomerulosclerosis, vacuole formations or inclusion of small granules of podocytes, appearance of foamy cells in the capillary lumina, eosinophilic deposits along the mesangial area, and focal atrophy of tubules with associated interstitial fibrosis. The halo, frequently seen in human FSGS, is due to detachment of visceral epithelium from basement membrane, however, did not appear in the experimental rat specimen. On the other hand, the foamy cells and hyalinization were more frequently noted in the rat series and even involved the arterioles. The mesangial proliferation never appeared in the rat series occasionally found in human FSGS. In conclusion, the pathogenesis of FSGS cannot depend solely on the hyperfiltration theory of hemodynamic derangement, but has complex impairment of visceral epithelium and cells forming the constituents of basement membrane.