[Objective] To observe the effect of cyclosporine A (CSA) on the activity and expression of MMP-2 and MMP-9 in renal tubular epithelial cells. [Methods] NRK52E cells were cultured until its reached confluent. Then NRK52E cells were exposed to different concentration of CSA (0, 0.42, 0.84, 4.2, and 8.4 μmoL/L) for 48 h or 72 h respectively. MMP-2 and MMP-9 activities were detected by gelatin zymography. The expression of MMP-2 and MMP-9 mRNA were detected by RT-PCR. [Results] MMP-2 activity and mRNA levels were decreased in a dose dependent manner after exposed to different concentration of CSA for 48 h or 72 h in NRK52E cells. Compared with control (CSA 0 μmoL/L), CSA 0.42, 0.84, 4.2, 8.4 μmoL/L decreased the MMP-2 activities to 27%, 24%, 11%, and 9% respectively; The differences are significant, P<0.05. But the MMP-9 activity and mRNA levels were increased after exposed to CSA for 48 h or 72 h in NRK52E cells. Compared with control group, CSA 4.2 μmoL/L exposure increased MMP-9 activity to 438% in 48 h, and 237% in 72 h; the differences are significant as well, P<0.05. [Conclusion] A dose-dependent decrease in the expression and activity of MMP-2, and the up-regulation of the expression and activity of MMP-9 by CSA in renal epithelial cells may related to CSA associated tubulointerstitial damage.