The purpose of the present study was to develop a new nanoparticulate formulation for delivery of tacrolimus to reduce its kidney distribution and functional nephrotoxicity. Tacrolimus (TAC)-loaded bovine serum albumin (BSA) nanoparticles (TAC-BSA-NPs) were prepared by emulsification-dispersion technique. The obtained TAC-BSA-NPs, with 189.50 ± 7.15 nm of diameter and −20.86 ± 0.45 mV of Zeta potential determined by DLS, were spherical in shape observed by TEM. The drug loading content and encapsulation efficiency were (1.7 ± 0.13)% and (85 ± 3.0)%, respectively. The in vitro release of TAC-BSA-NPs exhibited biphasic drug release pattern with an initial burst release and subsequently sustained release. Pharmacokinetic analysis displayed that TAC-BSA-NPs could enhance the drug blood level and prolong the circulation time in comparison to Prograf®. Meanwhile, compared with Prograf®, TAC-BSA-NPs could deliver less TAC to kidney and simultaneously reduce the functional nephrotoxicity of TAC to kidney. In conclusion, BSA nanoparticles might be a more safe carrier for delivery of hydrophobic drug TAC.