Objective The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with BDNF Val66Met polymorphism in PD.Methods Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics.Results The GG genotype in BDNF Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II.Conclusion Our findings demonstrate that the BDNF Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.