We investigated the effect of fat meal load (FML) on inflammatory factors during the process of atherosclerosis (ATH). Ten male New Zealand white rabbits (fed with high-fat meal for 12 weeks, and provided FML at the beginning (W1), as well as in the 4th, 8th, and 12th weeks, (W4, W8, and W12, respectively) were used in this study. Blood samples were collected after fasting and at 2, 4, 6, and 8 h after FML (T0, T1, T2, T3, and T4, respectively) to detect plasma endothelin-1 and interleukin (IL)-6, IL-8, and IL-10; ATH conditions in the abdominal aorta were observed ultrasonically. At W12, the animals were sacrificed and ATH conditions were detected by hematoxylin and eosin staining. After continuous high-fat feeding, fasting plasma endothelin-1 was increased in W4, W8, and W12, IL-8 was increased in W4 and IL-10 was increased in W4 and W8. After FML, endothelin-1 was significantly increased at W0-T2, and W12-T1, IL-8 was increased at W0-T1-3, W4-T1-2, and W8-T1-3, and IL-10 was increased at W0-T1-4, W4-T2-4, and W12-T1-2. During early ATH, inflammation was severe and clearly observed at 4-6 h after FML.