Thoracic aortic dissection (TAD) is a life-threatening disease that is characterized by an inflammatory response. Innate and cellular immunity has long been known to be involved in TAD, but the role of humoral immunity in the pathophysiology of TAD remains unknown. We administered the lysyl oxidase inhibitor beta-aminopropionitrile (BAPN; 1 g/kg/day) in 3-week-old male C57BL/6J mice for 4 weeks to establish an animal model of TAD. Animals that died were immediately dissected. Animals that survived were sacrificed on days 7, 14, and 28 after BAPN challenge. The incidence and rupture rates of BAPN-induced TAD were 90% (9/10) and 70% (7/10), respectively, at 28 days. Victoria blue-nuclear fast red staining of aortic tissue revealed elastic lamellae destruction and the formation of a false lumen in the BAPN group. Hematoxylin-eosin staining revealed the infiltration of both plasmacytoid mononuclear cells and polymorphonuclear inflammatory cells in TAD tissues. Enzyme-linked immunosorbent assay and immunohistochemistry indicated that plasma immunoglobin M (IgM) and IgG were elevated at 7, 14, and 28 days, and CD19-positive B cells infiltrated into the adventitia of aortic tissue in BAPN-treated mice. The transcriptional analysis showed an increase in the expression of B cell receptor signaling-associated genes. These results indicate that B cells and immunoglobulins might participate in the pathogenesis of TAD, suggesting that humoral immunity may be a possible therapeutic target for TAD.