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FK506-loaded solid lipid nanoparticles (FK506-SLNs) were prepared by a modified emulsification and low temperature solidification method and characterized by size analysis and entrapment efficiency.The influence of experimental factors such as lipid carriers, surfactant concentration, emulsification temperature and stirring velocity on particle size and entrapment efficiency were investigated to optimize the formulation.The feasibility of fabricating FK506-SLNs by this method was successfully demonstrated in this investigation.The SLNs were characterized for appearance, morphology, particle size, entrapment efficiency, zeta potential and in vitro release, and then they were incorporated in a carbopol hydrogel to determine the influence on the in vitro drug transdermal delivery.Commercial tacrolimus ointment served as a comparison.Excised full thickness rat skins were mounted on Franz diffusion cells and the formulations were applied for 48 h.Greater skin permeation of FK506 was detected from the SLNs hydrogel than from the commercial ointment.A higher FK506 stagnation amount was detected in the skins following SLNs hydrogel application than from the commercial ointment, which suggested a drug localizing effect.