Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin (THC) on thoracic aortic aneurysm and dissection (TAAD) in mice. Methods TAAD was induced in 3-week-old C57BL / 6J mice by oral administration of β-aminopropionitrile (BAPN) (diluted in drinking water, 1 g / (kg·d)).Eighty mice were divided randomly into Con, BAPN, BAPN + THC, and BAPN + THC + 3-TYP (SIRT3 inhibitor) groups (n = 20 mice per group). The survival rate of mice in each group was recorded after 4 weeks. The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining. Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin ( α-SMA ) and osteopontin ( OPN ) expression were detected by immunofluorescence staining. The production of reactive oxygen species (ROS) was measured by dihydroethidium staining and superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were determined using kits.Protein expression levels of matrix metalloproteinase (MMP) 2, MMP9, interleukin ( IL)-6, tumor necrosis factor (TNF)-α, nuclear factor erythroid 2-related factor 2 (NRF2), NADPH oxidase 2 (NOX2), α-SMA, OPN, sirtuin 3 ( SIRT3), Ac-SOD2, and SOD2 were measured by Western Blot. Results Mice in the BAPN + THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved (P<0. 05). Infiltration of CD68-positive macrophages and MMP2, MMP9, IL-6, and TNF-α expression levels were lower (P<0. 05), ROS generation, MDA content,and NOX2 expression in aortic tissue were also significantly decreased, while SOD activity and NRF2 expression were increased (P<0. 05). α-SMA expression was also increased, while OPN expression was reduced ( P<0. 05).SIRT3 expression was increased while the Ac-SOD2 / SOD2 ratio was decreased ( P<0. 01). Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway ( all P<0. 05). Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway, thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.