Abstract: Objective To observe the effects of norcantharidin (NCTD) on proliferation and fibronectin (FN) expression in human renal proximal tubular epithelial cell line (HK-2) induced by albumin, and to investigate the mechanism of NCTD in the prevention of renal interstitial fibrosis. Methods Appropriate NCTD concentration which did not significantly injure HK-2 cells was determined by cytotoxicity test. HK-2 cells were divided into 5 groups: control group (1640 group), albumin group (1640 + albumin 5g/L), and NCTD 0.5 mg/L, 1mg/L and 2.5mg/L groups (1640 + albumin 5g/L + NCTD 0.5, 1 or 2.5mg/L). HK-2 cells were incubated with respective concentrations of NCTD and albumin for 24 hours. Proliferation of HK-2 cells was determined by MTT, and FN protein in culture media by enzyme-linked immunosorbent assay (ELISA). FN mRNA in HK-2 cells was analyzed by RT-PCR. Results ①Cytotoxicity test showed that there were no significant differences in lactate dehydrogenase (LDH) concentration among NCTD 0.5 mg/L，1.0 mg/L and 2.5 mg/L groups as well as control group (P>0.05); ② MTT score was higher in albumin group (0.438+0.073) than in 1640 group (0.330+0.060) (P<0.05), but MTT score decreased to 0.327+0.080 in NCTD 2.5mg/L group (P<0.05, as compared with that of albumin group); ③FN protein was down-regulated in NCTD 2.5mg/L group (P<0.01, as compared with that of albumin group), and FN mRNA significantly decreased in NCTD 1mg/L and 2.5mg/L groups (P<0.01, as compared with that of albumin group). Conclusion NCTD inhibits the albumin-induced cell proliferation and FN over-expression in HK-2 cells.