【Objective】 To investigate the dynamic changes of local and systemic inflammatory responses after high-fat diet feeding of ApoE^-/- mice so as to establish the method to assess the recruitment of PKH26-labeled monocytes into atherosclerotic plaque. 【Methods】 ApoE^-/- mice that had received a high-fat diet (HFD) for 8 and 16 weeks were assessed for: ① atherosclerotic plaque burden (oil red O staining), ② aortic tissue inflammation (by RT-qPCR to detect aortic inflammatory factors and cells), ③ systemic inflammatory responses (by ELISA to measure plasma proinflammatory cytokine levels and flow cytometry to assess inflammatory cellular profile in the peripheral blood), and ④ recruitment of PKH26 labeled monocytes into atherosclerotic lesions (by confocal microscope). 【Results】 Compared to those in high-fat diet 8 weeks group, ApoE^-/- mice in high-fat diet 16 weeks group had more serious atherosclerosis in the whole aorta and aortic root (P<0.01); significantly up-regulated aortic mRNA levels of inflammatory factors CCL2, TNF-α and IL-1β (P<0.01); an increased number of aortic local macrophages (P<0.001); significantly increased protein expression of plasma CCL2 and TNF-α (P<0.01); and the increased percentage of peripheral blood monocytes (P<0.05). Moreover, the number of PKH26 labeled monocytes that migrated to aortic lesions were significantly higher in high-fat diet 16 weeks group (P<0.01). 【Conclusion】 High-fat diet promotes the severity of systemic and local inflammatory responses in ApoE knockout mice, which contributes to the migration of peripheral blood monocytes to atherosclerotic plaque.