Cyclosporine A (CsA) is a effective and widely used immunosuppressive agent. Nevertheless, its intense nephrotoxicity restricts clinical application. In this study, wistar rats were randomly divided into a control group, a low-dose group and a high-dose group. The rats in the low-dose group and those in the high-dose group were given CsA at a daily dose of 5 mg per kg and 100 mg per kg by gavage for 7 d respectively, while the control group was given distilled water of equal volume. The extent of renal impairment was evaluated by renal function assay, and urease and pathological observation. The results showed that the rats in the low-dose group did not suffer remarkable renal impairment, while the rats in the high-dose group did. Two-dimensional gel electrophoresis (2DE) was utilized to resolve the plasma protein profile. Six spots showing stable and significantly different expression were identified by MALDI-TOF-MS and ESI-TOF-MS/MS respectively, the two induced proteins were identified respectively as alpha-1-acid glycoprotein (AAG) and clusterin (CLUS), and the one inhibited was haptoglobin (Hp).