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. The in vitro viability experiment showed that the NP formulation could be 1.28, 1.38, 1.12 times more effective than Taxol(R) after 24, 48, 72 h incubation with MCF-7 human breast cancer cell line at 2.5 microg/mL paclitaxel concentration. In vivo evaluation confirmed the advantages of the TPGS-emulsified PLGA NP formulation versus Taxol in promoting oral bioavailability of paclitaxel. Such a NP formulation achieved more than 10 times higher oral bioavailability than Taxol, which resulted 9.74-fold higher therapeutic effect and 12.56-fold longer sustainable therapeutic time than Taxol. 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.