Objective To detect the effect of high fat diet and K / BxN serum on the distribution of immune cellsin ApoE gene knockout ( ApoE^{-/ -} ) mice. Methods ApoE^{-/ -} mice were fed with high fat diet (HFD) from 8 weeks of age,then the K / BxN serum whose anti-glucose-6-phosphate isomerase (GPI) antibodies were positive was injected intraperitoneallyonce a week, with each injection of 0. 2 mL, from 17 to 26 weeks of age. The control group was fed withordinary diet (CD) and injected the K / BxN serum in the same way. The level of blood lipid was analysed by ELISA, andthe ankle swelling was measured by vernier caliper before and after the K / BxN serum was injected intra-peritoneally. Thesplenocytes and bone marrow cells of ApoE^{-/ -} mice were isolated and stained by flow antibodies at 26 weeks of age, thendetected by flow cytometry. Results Serum LDL-C, TCHO and TG levels of ApoE^{-/ -} mice were significantly increasedbefore and after K / BxN serum was injected, and the areas of atherosclerotic plaques were significantly increased in aorticroots after K / BxN serum injected, suggested that whether K / BxN serum was injected, HFD could induce atherosclerosis of ApoE^{-/ -} mice, and the atherosclerotic symptom of ApoE^{-/ -} mice fed with HFD was more severe than the CD treated group.The ankle width and clinical scores showed that the ankle swelling of ApoE^{-/ -} mice was normal before K / BxN seruminjected. However, ApoE^{-/ -} mice fed with HFD had lower joint width and clinical score than ApoE^{-/ -} mice fed with CD after K / BxN serum injected. The flowcytometry analysis showed that HFD down-regulates CD3+ T cells and CD19+ B cells, upregulatesCD11b+ macrophages in splenocytes and bone marrow cells. Conclusions HFD down-regulates CD3+ T cells andCD19+ B cells, up-regulates CD11b+ macrophages in splenocytes and bone marrow cells, so aggravates the atherosclerosis and relieves arthritis of ApoE^{-/ -} mice.