Aim To investigate the role of Notch pathway in the anti-atherosclerotic effect of angiotensin-(1-7) (Ang-(1-7)). Methods Oxidized low density lipoprotein (ox-LDL) was used to induce macrophages to foam cells.At first, 10－7 mmol/L Ang-(1-7) and 10－5 mmol/L A-779 were pre-cultured with macrophages before ox-LDL administered solely or together in Ang-(1-7) group and A-779 group. Notch ligands, receptors and downstream product Hes1 were assayed by qRT-PCR and Western blot. Second, delta-like (Dll) 4.Fc was co-cultured with macrophages to activate Notch pathway, toll like receptor-4 (TLR-4), nuclear factor kappaB (NF-κB) and iNOS mRNA and protein were assayed by qRT-PCR and Western blot, proinflammatory cytokines interleukin 1beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) were assayed by using ELISA. Results Notch1, Notch2 and Dll1 mRNA levels were significantly decreased in ox-LDL group, whereas elevated in Ang-(1-7) group (P＜0.05). Meanwhile, Notch3, Notch4, Dll4 and Jagged2 mRNA levels were significantly increased in ox-LDL group, while reduced in Ang-(1-7) group (P＜0.05). There was no difference in Dll3 and Jagged1 mRNA levels between ox-LDL group and Ang-(1-7) group (P＞0.05). The downstream product of Notch pathway gene Hes1 was significantly activated by ox-LDL (P＜0.05), while decreased by Ang-(1-7) administrated (P＜0.05). Using Dll4.Fc to activate Notch pathway could increase the expressive levels of Hes1 and TLR-4, promote translocation of NF-κB from cytoplasm to nucleus, and stimulate inflammatory cytokines IL-1β, IL-6 and TNF-α secretion (P＜0.05). Ang-(1-7) could rescue this alternation significantly (P＜0.05). Co-treatment with A-779 can reverse the effect partially (P＜0.05). Conclusion Ang-(1-7) could alleviate TLR-4/NF-κB-induced inflammatory cytokines secretion in macrophages via regulating Dll4-associated pathway.