Objective To investigate the role of autonomic nervous function and the effect of royal jelly intervention on rabbit models of atherosclerosis (AS). Methods Eighteen healthy 3 - 4?month old male Japanese white rabbits were randomly divided into normal control (NC) group, high?fat high?sugar diet (HFHSD) group and royal jelly intervention (RJ) group, 6 rabbits in each group. The rabbits received high?fat and high?sugar diet for 12 weeks to induce atherosclerosis model. At the same time, the RJ group was orally given 200 mg/ kg royal jelly daily, twice a day, for consecutive 12 weeks. The plasma levels of total cholesterol (TC), triglyceride (TG), low?density lipoprotein cholesterol (LDL?C) and high?density lipoprotein cholesterol (HDL?C), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) were detected. The electrocardiogram and blood pressure were monitored, and the heart rate variability (HRV) and baroreflex sensitivity (BRS) were analyzed. The pathological changes in the abdominal aorta tissues were observed using H&E and Sudan IV staining, respectively. Results Compared with the NC group, the levels of serum lipids in the HFHSD group were significantly increased ( P < 0. 05). The lipid deposition and atherosclerotic plaque sizes in the abdominal aorta were significantly increased ( P < 0. 05). The plasma SOD and NO levels were decreased and the MDA content was increased ( P < 0. 05, P < 0. 01). The reduction of cardiac function was accompanied by a decrease of HRV and BRS values ( P < 0. 05, P < 0. 01). Compared with the HFHSD group, RJ significantly improved the above indicators. Conclusions High fat and high sugar diet can lead to cardiac autonomic nervous dysfunction and to further form atherosclerosis in rabbits. Royal jelly intervention can regulate cardiac autonomic nervous function and delay the development of atherosclerotic lesions.