Objective To compare the Bama minipig and Juema minipig models of high altitude multi-organ dysfunction syndrome. Methods Six plateau-origin Juema minipigs and plain-origin Bama minpigs in each group received intravenous infusion of 0.35 mg/kg lipopolysaccharide (LPS), respectively. Blood samples were taken at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h and 72 h after LPS infusion. Routine blood test was performed, blood CK, AST, ALT, TBIL, CRE were assayed, and histopathological examination of the lung tissues was performed at 24 h, 48 h after LPS infusion. Results The mortality of Bama minipigs was 33.3%, higher than that of 16.7% of Juema minipigs. The trend of physiological and biochemical changes was similar, but was milder in the Juema minipigs than in Bama minipigs. The lung injuries of the Bama minipigs at 24 h and 48 h were more severe than those in the Juema minipigs. Conclusions Both Bama and Juema minipig models of high altitude multi-organ dysfunction syndrome can be successfully established. Juema minipig models can be more closely and safely established, due to its own plateau biological properties, and avoid the influence by extrinsic injurious effects of plateau environment.