Abstract: Objective To investigate the induction of abdominal aortic aneurysm by DOCA plus high salt at different time points and the undeRLying molecular mechanism. Methods Ten-month-old C57BL/ 6J mice were divided into two groups: a high-salt group (HS) and a DOCA plus high-salt group (DOCA+HS). Each group received the designated treatments for 1 week, 2 weeks, and 3 weeks. At the end of treatment, the mice were anesthetized with isoflurane followed by ultrasonography and aorta collection to observe abdominal aorta expansion and aneurysm formation. H&E staining, Masson’ s staining, and elastic fiber staining were performed to detect pathological changes, collagen deposition, and elastic fiber fragmentation, respectively. Immunohistochemistry was used to detect abdominal aortic inflammatory cell infiltration, and RT-PCR was used to detect the mRNA expression of inflammatory and anti-inflammatory factors. RNA sequencing was conducted to analyze the differentially-expressed genes and the enrichment signaling pathways of these genes in the arterial tissues of the two groups of mice after 3 weeks of treatment. Results Compared with the HS group, DOCA+ HS treatment for 1 week did not induce the formation of abdominal aortic aneurysms in mice, but after 2 weeks of treatment, the mice began to form aortic aneurysms. The incidence of aortic aneurysm was 44% at week 2 and 65% at week 3. With increased duration of DOCA+HS treatment, collagen deposition in the abdominal aorta increased, and elastic fiber fragmentation was observed. Meanwhile, high inflammatory cell infiltration (mainly macrophages and T cells) was observed in the abdominal aorta of mice after treatment with DOCA+HS for 2 weeks and 3 weeks. The mRNA levels of inflammatory factors increased significantly, while the mRNA levels of anti-inflammatory factors decreased. Additional transcriptome sequencing result showed that the differentially-expressed genes in the two groups of mice after 3 weeks of treatment were enriched mainly in the immune system and metabolic pathways, and that levels of the key molecule PSGL-1, which mediates leukocyte adhesion, increased significantly after 3 weeks of DOCA+ HS treatment. Conclusions DOCA+ HS treatment can induce abdominal aortic aneurysm formation in mice after 2 weeks of therapy. PSGL-1 and its mediated inflammation may play important roles.