Aim To explore the mediating effect of Th17/Treg cell functional axis on arteriosclerosis induced by depressive stress in older adults. Methods From May 2018 to August 9,9 older individuals aged 60 and above were enrolled in community in Jinan area, Shandong. Geriatric depression scale (GDS) was used to evaluate depressive stress of the participants. According to the quintile of the GDS scores, participants were divided into low depressive stress group (n=349) and high depressive stress group (n=190). Common carotid intima-media thickness (CCA-IMT) and carotid-femoral pulse wave velocity (cfPWV) were used to assess arteriosclerosis and stiffness. The serum level of high sensitivity C-reactive protein (hs-CRP) and the frequencies of peripheral blood Th17 and Treg cells and relative cytokines were detected. Results Compared with the low depressive stress group, CCA-IMT, cfPWV, Th17 cell frequencies, the levels of hs-CRP, interleukin-17 (IL-17), tumor necrosis factor alpha (TNF-α), IL-6 and IL-23, the expression of retinoic acid receptor-related orphan receptoryγt (RORγt) mRNA, and the ratio of Th17/Treg cells in the high depressive stress group increased by 24.58%, 18.22%, 51.59%, 44.79%, 77.60%, 55.94%, 61.49%, 41.13%, 72.11% and 150.00% respectively; while the Treg cell frequencies, the levels of IL-10 and transforming growth factor β1 (TGF-β1), and the expression of forkhead box protein P3 (Foxp3) mRNA decreased by 36.53%, 32.96%, 27.65% and 35.35% respectively (all P＜0.001). After adjusting for confounding factors, GDS score was independently and positively correlated with CCA-IMT, cfPWV, Th17 cell frequencies, hs-CRP, IL-17, TNF-α, IL-6, IL-23, RORγt mRNA expression, and Th17/Treg cells ratio, whereas it was independently negatively correlated with Treg cell frequencies, IL-10, TGF-β1, and Foxp3 mRNA expression (all P＜0.001). The results of Hayes Process analysis showed that hs-CRP, Th17/Treg cells ratio, IL-17, and IL-10 played significant mediating roles in the correlations of GDS with CCA-IMT and cfPWV. Conclusions Depressive stress is an independent risk factor for arteriosclerosis in the elderly. Chronic inflammation may be an important mediating effector in the process of arteriosclerosis induced by depressive stress.