Aim: To clarify the role of leukocyte subsets in the development of glomerulosclerosis (GS) and interstitial lesions which may contribute to the prognosis of membranous nephropathy (MN), we investigated infiltrating cells in both glomeruli and interstitium in biopsy specimens. Methods: Forty-one cases of MN were divided into two groups: MN with segmental GS (MN+GS; n = 21) and MN without GS (MN–GS; n = 20). There was no significant difference between both groups regarding clinical data at the time of the renal biopsy. The cells were analyzed with a three-layer indirect immunoperoxidase method using monoclonal antibodies against leukocyte common antigen, T cells, B cells, and monocytes/macrophages (Mo/Mφ). Results: Renal function tended to deteriorate during the final follow-up period in group MN+GS, but not in group MN–GS. The number of glomerular and interstitial leukocytes in group MN+GS were significantly higher than those in group MN–GS. Leukocytes were mostly Mo/Mφ in the glomerulus, while T cells and Mo/Mφ were predominant in the interstitium. In group MN+GS, there was a significant correlation in number of Mφ (CD68+) between glomeruli and interstitium, but not in group MN–GS. Conclusion: The results suggest that Mo/Mφ may play an important role in the development of segmental GS and interstitial lesions in MN which may be responsible for the incurability and poor prognosis.