Objective To observe the changes in blood lipid and inflammatory cells in Wuzhishan (WZS)minipigs and Tibetan minipigs exposed to a high-fat diet environment, and to analyze the expressions of coronary arterydisease-related blood lipid and inflammatory susceptibility genes. Methods Five male WZS minipigs and five Tibetanminipigs were selected for feeding with a high-fat diet for six consecutive months. Blood lipids and blood routine examinationwere performed monthly, and venous blood was taken before and 6 months after high-fat feeding to determine the gene andprotein expression levels of LDLR, LPL, PCSK9, ApoAV, 5-LO, FLAP, MMP-9, ICAM-1 and VCAM-1 in peripheralleukocytes, as well as the levels of CRP and TNF-α. Thoracic aorta samples were taken for pathological examination afterhigh-fat feeding for 6 consecutive months. Results After high-fat diet feeding, the levels of TC, HDL-C, and LDL-C inthe two minipigs were significantly increased ( P <0. 01), and WBC, NEUT% and MONO% in the Tibetan minipigs as wellas MONO% in the WZS minipigs tended to be increased ( P >0. 05). TC and LDL-C levels in the WZS minipigs were higherthan those in the Tibetan minipigs, whereas WBC, NEUT% and MONO% in the Tibetan minipigs were much higher thanthose in the WZS minipigs ( P <0. 05, P <0. 01). After high-fat feeding for 6 months, there were obvious atherosclerotic(AS) plaques in the two minipigs, but the degree of AS lesions in the Tibetan minipigs was more serious. The mRNA andprotein expressions of LDLR and ApoAV in the WZS minipigs were markedly decreased ( P <0. 05, P <0. 01), whereas themRNA expressions of PCSK9 and LPL were markedly increased ( P <0. 05, P <0. 01). The mRNA and protein expressionsof LPL in the Tibetan minipigs were obviously increased ( P <0. 01). Moreover, the mRNA expressions of 5-LO, FLAP,ICAM-1 and VCAM-1, and protein expression of 5-LO in the WZS minipigs were significantly increased ( P <0. 05, P <0. 01). mRNA and protein expressions of FLAP, MMP-9, ICAM-1, and VCAM-1 in the Tibetan minipigs were markedlyincreased ( P <0. 05, P <0. 01). Moreover, mRNA and protein expressions of MMP-9, ICAM-1, and VCAM-1 in Tibetanminipigs were higher than those in the WZS minipigs, whereas mRNA and protein expressions of 5-LO were lower.Conclusions WZS and Tibetan minipigs have various degrees of dyslipidemia and inflammation under a high-fat dietenvironment. Significant heterogeneity exists in CAD-related blood lipids and inflammatory susceptibility genes. Theexpressions of LDLR, PCSK9, and 5-LO in the peripheral leukocytes are more affected in WZS minipigs, while LPL,ICAM-1, VCAM-1, and MMP-9 in the peripheral leukocytes are more affected in Tibetan minipigs.