Glial cell line-derived neurotrophic factor (GDNF) is a potent agent for treating Parkinson's disease (PD). Microbubbles (MBs) have been exploited as a carrier for GDNF delivery with focused ultrasound (FUS) destruction. However, GDNF supplementation only relieves PD symptoms rather than cure it. Thus, design of an endogenous GDNF generative mechanism is an urgent concern for novel PD treatment. Here, we synthesized a cationic MBs (cMBs) with high GDNF plasmid (GDNFp) binding to achieve blood-brain barrier disruption (BBBD) with FUS, and currently enhance the GDNFp transfection for PD therapy. PD lesions were established by implanting 6-hydroxydopamine into left brain of rats. A 1-MHz FUS (0.7 MPa, duty factor = 5 %, PRF = 1 Hz, sonication time = 90 s) was sonicated at striatum and substantia nigra after GcMBs injection. Sites of gene expression were confirmed by firefly luciferase gene-loaded cMBs (LcMBs) with bioluminescence imaging, individually. The motor behavior and dopamine (DA) levels of the treated rats were traced to estimate treatment outcome. Result showed that the positively charge of cMBs (+39.48 ± 9.28 mV) made them significant for DNA binding. With FUS, GcMBs provided sufficient BBBD area for enhanced gene transfection in PD lesion. Bioluminescence data showed that the released Luc-gene expressed started from 24 h after treatment. The GDNF level of PD rats restored following the combing treatment (66.6 % of recovery). The treatment reduced rotations by 92.2 ± 5.7%, and improved of DA levels by 164.9 ± 1.23%. This study confirmed that GcMBs with FUS provides a novel strategy for local gene therapy in PD rats.