Objective To investigate the role of autonomic nervous function in rabbit model of atherosclerosis (AS) and the intervention effect of royal jelly. Methods 18 male Japanese white rabbits were randomly divided into normal control (NC) group, high-fat high-sugar diet (HFHSD) group and royal jelly treatment (RJ) group, 6 rabbits in each group. The rabbits were received high-fat and high-sugar diet for 12 weeks to induce AS model, at the same time, the RJ group was orally received 200 mg/kg of royal jelly daily, twice a day. After 12 weeks, the levels of plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) were detected. Meanwhile, 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 by H&E and Sudan IV staining, respectively. Results Compared with the NC group, the levels of serum lipids in the HFHSD group were significant increased (P<0.05). The lipid deposition and atherosclerosis plaque sizes in the abdominal aorta were increased significantly (P<0.05). The plasma SOD, NO level 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 could significantly improve these above indicators. Conclusions High fat and high sugar diet can lead to cardiac autonomic nervous dysfunction and further to form AS in rabbits. Royal jelly intervention can adjust cardiac autonomic nervous function and delay AS lesions.