Sarcoma represents one of the most common malignant tumors with poor treatment outcomes and prognosis. Docetaxel (DTX) is acknowledged as one of the most important chemotherapy agents. The aim of this study was to improve the efficacy of docetaxel by incorporation into the mPEG-PLA nanoparticle (DTX NP) for the treatment of sarcoma. The DTX NP was prepared by emulsion solvent diffusion method and the prescription and preparation process were optimized through a single factor experiment. The optimized DTX NP was characterized by drug loading, encapsulation efficiency, drug release, etc. Then, the pharmacokinetics was conducted on rats and tumor-bearing ICR mice. Finally, the anti-tumor efficacy of DTX NP with different dosages was evaluated on tumor-bearing ICR mice. The optimized DTX NP was characterized by around 100 nm sphere nanoparticles, sustained drug release with no obvious burst drug release. Compared with DTX injection, the AUC of DTX NP increased by 94.7- and 35.1-fold on the rats and tumor-bearing ICR mice models, respectively. Moreover, the intra-tumoral drug concentration increased by 5.40-fold. The tumor inhibition rate of DTX NP reached 94.66%, which was 1.24 times that of DTX injection (76.11%) at the same dosage, and the bodyweight increase rate was also higher than the DTX injection. The study provided a DTX NP, which could significantly improve the bioavailability and therapeutic efficacy of DTX as well as reduced its toxicity. It possessed a certain prospect of application for sarcoma treatment.