Aim To study the effect of maternal high-fat diet during pregnancy on endothelial to mesenchymal transition of aortic vessels in adult offspring. Methods The pregnant mice were randomly divided into normal diet group and high-fat diet group, and the offspring mice were fed normally for 16 weeks after the mother gave birth. Western blot and RT-qPCR were used to detect the expression and transcription of related proteins, and immunofluorescence and immunohistochemical staining were used for pathological analysis. Results Compared with the offspring of maternal normal diet during pregnancy, the expressions of vascular inflammatory factors, macrophage infiltration, monocyte-endothelium adhesion were significantly increased in the offspring of maternal high-fat diet (OHF) during pregnancy (P＜0.05). Vascular endothelial nitric oxide synthase (eNOS) activity, nitric oxide (NO) level were dramatically reduced (P＜0.05). Immunofluorescence results showed reduced endothelial cell marker CD31 and increased mesenchymal marker α-smooth muscle actin (α-SMA) in OHF. Western blot analysis further confirmed the results, which showed that maternal high fat diet reduced vascular endothelial-cadherin (VE-cadherin) and CD31 and increased α-SMA and Vimentin in the offspring (P＜0.05). The maternal high fat diet increased the extracellular matrix protein disposition and transforming growth factor beta (TGF-β)/Smad signaling in endothelium (P＜0.05). Moreover, the maternal high fat diet reduced Kruppel-like factor 2 (KLF2)expression by 76% in mRNA level and 59% in protein level (P＜0.05). Conclusion Maternal high-fat diet during pregnancy lead to a transition of endothelial to mesenchyme in the offspring aorta. The results provide a clue for prevention of vascular disease in early stage.