To develop a novel self-nanoemulsifying drug delivery system (solid SNEDDS) with better oral bioavailability of tacrolimus, the solid SNEDDS was obtained by spray-drying the solutions containing the liquid SNEDDS and colloidal silica. Its reconstitution properties were determined and correlated to solid state characterisation of the powder. Moreover, the dissolution and pharmacokinetics in rats was done in comparison to the commercial product. Among the liquid SNEDDS formulations tested, the liquid SNEDDS comprised of Capryol PGMC, Transcutol HP and Labrasol (10:15:75, v/v/v) presented the highest dissolution rate. In the solid SNEDDS, this liquid SNEDDS was absorbed in the pores and attached onto the surface of the colloidal silica. Drug was present in the amorphous state in it. The solid SNEDDS with 5% w/v tacrolimus produced the nanoemulsions and improved the oral bioavailability of tacrolimus in rats. Therefore, this solid SNEDDS would be a potential candidate for enhancing the oral bioavailability of tacrolimus.