OBJECTIVE: To observe the expression of nephrin in hepatitis B virus-associated membranous nephropathy (HBV-MN), and investigate the impairment and significance of podocyte in HBV-MN. METHODS: The protein expression of nephrin in renal biopsy specimens in 35 patients, who were diagnosed as HBV-MN by renal biopsy, was determined by immunohistochemistry and tested by semi-quantitative method. The relationship between the expression of nephrin and clinicopathological data was analyzed. RESULTS: Among the 35 cases with HBV-MN, 6 were in MN phase I, 20 in MN phase II and 9 in MN phase III. A strong intensity expression of nephrin in normal glomerulus was found along capillary loop of glomerulus, while its expression in HBV-MN patients decreased obviously. There was no significantly difference in the expression of nephrin among the different stages of HBV-MN (P > 0.05). The expression of nephrin in different clinical types was significantly different(P < 0.05). The expression of nephrin in patients with nephrotic syndrome was significantly lower than that in patients without nephrotic syndrome (P < 0.01). The expression of nephrin in different grades of 24-hour urinary protein excretion quantity was significantly different(P < 0.05). There was negative correlation between the expression of nephrin and 24-hour urinary protein excretion quantity(r = -0.378, P < 0.05). In the patients with HBV-MN phase II, the expression of nephrin in patients with nephrotic syndrome was also significantly lower than that in patients without nephrotic syndrome (P < 0.01). CONCLUSIONS: The damage of podocytes emerge in the early stage of HBV-MN and the expression of nephrin in HBV-MN patients, especially in patients with nephrotic syndrome, are significantly down regulated. The descended expression of nephrin in HBV-MN patients may promote the production of proteinuria.