The difference in immunoregulatory effects between sirolimus and tacrolimus on kidney transplantation remains unclear. In this study, a total of 18 living-donor-related kidney transplant recipients received sirolimus (n = 8) or tacrolimus (n = 10) treatment. Kidney function, acute rejection, peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs), CD19(+)CD5(+)CD1d(+) regulatory B cells (Bregs), and panel reactivity antibody were analyzed after one and three years. Th1/2 cell polarization was also determined at one year. The proportion of Tregs in the recipients receiving tacrolimus significantly decreased to 3.69% and 2.49% at one and three years, respectively, compared to 6.59% in controls, whereas the proportion in the recipients receiving sirolimus remained at 6.67% and 5.66%, respectively. However, no differences in kidney function, acute rejection, proportion of Bregs, panel reactivity antibody, or the frequencies of Th1/2 cells were identified. In conclusion, unlike tacrolimus, sirolimus maintains the proportion of Tregs in kidney transplant recipients. (C) 2015 Elsevier Inc. All rights reserved.