Chronic allograft nephropathy (CAN) is an important cause of renal graft loss and diminished renal function after renal transplantation. The histologic characteristic of CAN is intimal hyperplasia, tubular atrophy, and interstitial fibrosis stimulated by profibrotic cytokines. The pathogenesis of CAN is complex and incompletely understood. Calcineurin inhibitor-induced nephrotoxicity such as cyclosporine A (CsA) is believe to be a factor that lead to the development of CAN. The increased expression of TGF-1, a key factor of fibrogenesis, is one predominant factor in the pathogenesis of immunosuppressive-induced nephropathy. In this study we evaluate the effect of intervention by CsA dose reduction with the addition of sirolimus (SRL) or mycophenolate mofetil (MMF) on the declination of creatinine clearance (CCr) in patients with early CAN. In addition, serum TGF-1 level before and after intervention are examined. Methods. Fourteen patients with early CAN (defined as a slowly progressive decline in renal function with serum Cr higher than 50% of baseline but less than 2.5 mg/dL and Banff class I CAN histology) were enrolled. CsA doses were reduced in all cases and adjusted to maintain whole blood trough level less than 100 ng/ml. MMF was added for patients who received double immunosuppressive regimen (prednisolone + CsA). SRL was added and MMF was stopped for patients who were already prescribed MMF. The rate of CCr declination were calculated by analysis the slope of regression line between 1/Cr over time and between CCr from MDRD formular over time. Serum TGF-1 level was examined by elisa method. Statistical analysis was performed using Wilcoxon signed rank test. Results. The mean period after renal transplantation before CsA dose reduction was 77 months (111-216). Eight patients (57.14%) received SRL and six patients (42.86%) received MMF. The mean follow-up period after CsA dose reduction was 17 (7-22) months. There was a significant improvement in mean SD of the rate of CCr declination before and after CsA dose reduction from minus 0.260.17 to plus 0.17 0.45 mL/min/month by analyzing 1/Cr and from minus 0.220.13 to plus 0.100.33 mL/min/month by analyzing MDRD (P=.002). There was no significantly elevation of serum TGF-1 level before and after CsA dose reduction (36.7229.57 vs 45.4526.08 ng/mL; P=.074). Conclusion. We conclude that CsA dose reduction with the addition of SRL or MMF can significantly improve the rate of CCr declination in patients with early CAN. This intervention is also associated with stabilization of serum TGF- 1 level