Objective · To prepare the nanoparticles encapsulating PTX with organic biodegradable poly (lactic-co-glycolic acid)-monomethoxypoly (ethylene glycol) (PLGA-mPEG) as skeleton, and then to verify its ultrasound contrast enhanced imaging in superficial implantation tumor of pancreatic cancer and its antitumor effect in vitro. Methods · PTX-PLGA-mPEG (PTX-NPs) were prepared by double emulsion method. The preparation conditions were optimized through the design of four factors three levels orthogonal test with entrapment efficiency and loading drug efficiency as examining indexes in order to obtain optimum process parameters. Average particle size and electrical potential of the prepared PTX-NPs were examined by nano particle size and zeta potential analyzer. Size, morphology, distribution, and reunion were detected by transmission electron microscope (TEM). Ultrasound contrast enhanced imaging of PTX-NPs was observed in vitro and in superficial implantation tumor of pancreatic cancer in nude mice. Antitumor effect in vitro of PTX-NPs was detected by CCK-8 test. Results · PTX-NPs were prepared successfully. Entrapment efficiency and loading drug efficiency were (91.32±3.25)% and (2.666±0.092)%, respectively. The average size was (80.6±3.8) nm and the potential was (-13.4±1.5) mv. The morphology of PTX-NPs under TEM was spherical with excellent dispersion and no aggregation. The particles also showed a good image in vitro and in vivo. The result of CCK-8 test demonstrated that PTX-NPs significantly reduced survival rate of pancreatic carcinoma cells, and ultrasound (US) or targeted ultrasound microbubble (UTMD) given at the same time could further decrease the cell survival rate. Conclusion · PTX-NPs are good at ultrasound contrast enhanced imaging in superficial implantation tumor of pancreatic cancer. In vitro PTX-NPs have certain anti-tumor effect, which can be enhanced by US and UTMD.