Aim To investigate the mechanism of interleukin-35 (IL-35) in atherosclerosis, we observed the influence of IL-35 in atherosclerosis progression and the serum level variation of its related inflammatory factors, interleukin-10 (IL-10), transforming growth factor β (TGF-β) and IL-17, by establishing the animal models of atherosclerosis in ApoE－/－ mice. Methods 24 ApoE－/－ male healthy mice (8 weeks old) were randomly divided into three groups:control group, atherosclerosis group and IL-35 treatment group (every mouse received intraperitoneal injection of IL-35 (1.2 mg/kg, qd) after providing basic food for a week). Control group were provided basic food, the other two groups were provided fatty food to establish the animal models of atherosclerosis. The blood specimen and aorta vascular tissues were collected after 16 weeks. Hematoxylin-eosin staining was used to observe the atherosclerotic plaque formation, and intima-media thickness was investigated. Expression of IL-10, TGF-β and IL-17 in aortic arteries was detected by immunohistochemical staining. Enzyme-linked immunosorbent assay ( ELISA) method was used to detect the expression level of IL-10, TGF-β and IL-17 in mice serum. Results Compared with the control group, atherosclerotic plaque in atherosclerosis group was obviously formed, and the intima-media was obviously thickened (P ＜0.01), the expression of IL-10 in aortic arteries were significantly increased(P＜0.05), while no changes were found in the expression of TGF-β in aortic arteries(P＞0.05), and the serum levels of IL-10 and TGF-β were significantly decreased (P＜0.05), the expression of IL-17 in aortic arteries and the serum levels were significantly increased(P＜0.05). Compared with the atherosclerosis group, atherosclerotic plaque in IL-35 treatment group were improved, and the intima-media was obviously thinned (P＜0.01), the expression of IL-10 and TGF-β and the serum levels were significantly increased(P＜0.05), while the expression of IL-17 and the serum levels were significantly decreased(P＜0.05). Conclusion IL-35 may retard the pathogenesis of atherosclerosis by down-regulating the levels of inflammatory chemokines IL-17, up-regulating the levels of anti-inflammatory chemokines IL-10 and TGF-β.