Abstract: In this paper, silymarin nanoemulsions(SM-NE)were prepared based upon PC/Tween 80 system, and adsorption of lactoferrin(LF)absorbed onto the surface of silymarin nanoemulsions via electrostatic interaction resulted in the formation of lactoferrin-modified silybin nanoemulsions(LF-SM-NE). SM-NE and LF-SM-NE were characterized in terms of the shape, diameter, zeta potential, and entrapment efficiency. In addition, in vivo absorption of SM-NE and LF-SM-NE following oral dosing was investigated by the application of LC-MS/MS in the determination of silymarin in blood sample. The results showed that the saturated adsorption of Lf at the surface of the SM-NE occurred at LF concentration of 0. 15 mg/mL and the incubation time of 4 h. LF-SM-NE were spherical with average particle size of(257±5. 9)nm, zeta potential of -(33. 1±1. 5)mV, entrapment efficiency(96. 9±1. 9)% and drug loading(3. 90±0. 12)%. Compared with those of SM-NE, LF-SM-NE significantly increased drug levels of LF in rats were observed after dosing of LF-SM-NE, and both of c_max and AUC were increased by approximately 2-fold. In summary, LF-SM-NE could improve oral drug absorption of LF in rats. The approach of enhancement in oral absorption of the nanoemulsions shows a promise for the application.