The objective of this investigation was to develop nanostructured lipid carriers (NLCs) of tacrolimus by the hot homogenization technique by sonication. NLCs are commonly prepared by emulsification and lyophilization. The feasibility of fabricating tacrolimus-loaded NLCs was successfully demonstrated in this study. The developed NLCs were characterized in terms of their particle size, zeta potential, entrapment efficiency (EE) of tacrolimus, and morphology. Studies were conducted to evaluate the effectiveness of the NLCs in improving the penetration rate through hairless mouse skin. Tacrolimus-loaded NLCs were found to have an average size of $123.4{pm}0.3;nm$, a zeta potential of $-24.3{pm}6.2;mV$, and an EE of 50%. In vitro penetration tests revealed that the tacrolimus-loaded NLCs have a penetration rate that is 1.64 times that of the commercial tacrolimus ointment, Protopic$^{(R)}$.