Background: Aortic aneurysm (AA) is one of the most common causes of sudden death among elderly people. Although AA can be detected by non-invasive imaging techniques, there are no pharmacological treatments currently available to prevent progression at any stage of the disease. In this study we will explore the expression of inhibitor of nuclear factor kappa-B kinase epsilon (IKKε) in AA and its potential underlying molecular mechanism in AA. Materials and methods: Human aortic tissue was taken from 14 patients who underwent surgical repair of AA for the AA group and another 11 patients with normal aorta who underwent aortic valve replacement surgery for the control group. After excision, we used haematoxylin-eosin staining, Masson staining, immunohistochemistry analysis and Western blot analysis to observe the expression, location and morphological changes of the IKKε, P50 and the extracellular matrix within the AA. Results: In the AA group, haematoxylin-eosin staining revealed a loss of medial integrity and inflammatory cell infiltration. Masson staining confirmed the degradation of the extracellular matrix in the AA group. Immunohistochemistry analysis showed increased infiltration of inflammatory cells and up-regulation of proinflammatory cytokines in the AA group when compared to the control group. Based on immunohistochemistry and Western blot analysis, there was clearly over-expression of IKKε, P50 and MMP2 in AA group, mainly in the intrinsic aortic cells of the media. Conclusions: The over-expression of IKKε may play an important role in the origination and progression of AA and might be a vital target for their treatment. (Folia Morphol 2017; 76, 3: 372–378)