Abstract: OBJECTIVE To study on the effectiveness and safety of flexible nano liposome mediated brain derived neurotrophic factor (BDNF) for the treatment of Parkinson disease by nasal administration. METHODS Flexible nano liposome of BDNF(BDNF-FNL) was prepared by injection. The Parkinson disease model rats were established and the successful model rats were randomly divided into three groups: model group, BDNF solution group, BDNF flexible nano liposome group, and using normal rats as control group. After drug was intranasal administrated, the content of BDNF in brain was measured in 0.5, 1, 1.5, 2 h, respectively. The pathological change of nasal mucosa was used to preliminary judgment of the safety of intranasal administration. The dopamine neuroreparable effects of Parkinson disease model rats was evaluated by the behavioral changes of experimental group rats, the immune positive neurons changes of substantia nigra TH, and the content changes of 3 monoamine neurotransmitters of brain striatum (DA, DOPAC and HVA). RESULTS The BDNF concentration of brain tissue of BDNF-flexible nano liposome group was about 3 times than BDNF solution group. Flexible nano liposome was high security through intranasal administration with no significant damage to the nasal mucosa. The behavior of rats was improved in BDNF flexible nano liposome group which were better than BDNF solution group. TH immunohistochemical results showed that flexible nano liposome could better mediate BDNF enter the brain and play the protective effect on DA neurons. And the contents of 3 kinds of monoamine neurotransmitters in rats’ striatum of BDNF flexible nano liposome group were apparently higher than that in BDNF solution group and model group. CONCLUSION Flexible nano liposome can mediate BDNF through nose to brain and play a repair action on dopamine neurons in Parkinson disease model rat, and shows good security of nasal mucosa.