Objective To explore the preparation of a new type BDNF liposome nanoparticles-loaded lipid ultrasound microbubble contrast agent (BDNF-UMCA) . Methods Ultrasound microbubbles contrast agent (UMCA) were prepared by adding a certain proportion of DPPG-PEG (2000) -Biotin based on "Zhifuxian" using cryochem and mechanical agitation method, BDNF-UMCA were prepared by coupling with biotinylated BDNF-loaded liposome nanoparticles via streptavidin; its physicochemical properties and the drug loading, entrapment efficiency, stability and acoustic characteristics in vivo were tested. Results The BDNF-UMCA had the average diameter of 4.2 ± 0.79 m, concentration of 1.02 × 10₉/ml, and the total drug content of 1.18 ± 1.96 mg/mL, the entrapment efficiency of 71.6 ± 2.6%. The average particle size and entrapment efficiency of BDNF-UMCA were not significantly changed at 4℃; the average particle size of BDNF liposome nanoparticle increases gradually over time at 24℃, there were statistically significant difference at 1, 3, 5 7 compared with initial particle size (all P<0.05); the entrapment efficiency were no statistically significant difference at each time (all P>0.05). BDNF-UMCA can significantly enhance the contrast imaging of experimental animal liver, having the average peak strength of 21.4 ± 0.9 dB and the average peak time of 4.7 ± 0.4 s. Conclusions Using Biotin-avidin conjugation method can be successfully prepared BDNF liposome-loaded ultrasound microbubbles contrast agents as a tool for targeted imaging and drug release through blood brain barrier.