This work evaluates the effects of paclitaxel loaded polymeric nanoparticles (NPs) composed of poly(D,L-lactic-co-glycolic acid) (PLGA) with vitamin E TPGS as emulsifier for oral chemotherapy. NPs prepared by a modified solvent extraction/evaporation technique were observed in spherical shape of 200-300 nm diameter with a high drug encapsulation efficiency (EE) of 80.9%. The TPGS-emulsified PLGA NPs formulation of paclitaxel was found of great advantages over that of Taxol 1 . The in vitro viability experiment showed that the NP formulation could be 1.28, 1.38, 1.12 times more effective than Taxol 1 after 24, 48, 72 h incubation with MCF-7 human breast cancer cell line at 2.5 mg/mL paclitaxel concentration. In vivo evaluation confirmed the advantages of the TPGS-emulsified PLGA NP formulation versus Taxol 1 in promoting oral bioavailability of paclitaxel. Such a NP formulation achieved more than 10 times higher oral bioavailability than Taxol 1 , which resulted 9.74-fold higher therapeutic effect and 12.56-fold longer sustainable therapeutic time than Taxol 1 . The present proof-of-concept experimental data proved that the formulation of vitamin E TPGS emulsified PLGA NPs is a promising approach for paclitaxel oral administration. Oral chemotherapy by NPs formulation is feasible.