Objective: To understand the histopathological and ultrastructural pathology changes of great gerbils in the Junggar Basin to Yersinia pestis infection. Methods: Forty captured great gerbils from the Junggar Basin that tested negative for anti-F1 antibodies were infected. The Y. pestis strain 2504, isolated from a live great gerbil in the natural plague foci of the Junggar Basin in 2005 with a median lethal dose (LD₅₀) of <10 CFU/ml, was used in this study. Forty great gerbils were divided into seven infection groups and were subcutaneously infected with 7.4×10⁵, 7.4×10⁶, 7.4×10⁷, 7.4×10⁸, 7.4×10⁹, 7.4×10¹⁰, or 3.0×10¹¹ CFU/ml of 2504. One milliliter of physiological saline was injected in the noninfected group as a control. We collected the liver, spleen, heart, and lung from all animals for histopathologic and ultrastructural pathology examination. Results: Great gerbils in the 7.4×10⁸-3.0×10¹¹ CFU/ml groups did not survive and exhibited pathological changes and altered ultrastructural pathology. The liver tissue of infected great gerbils showed spotty necrosis and fatty degeneration, intranuclear canaliculi with increased hepatocytes, and uneven distribution of organelles. Additionally, reactive proliferation of lymphoid tissue in the spleen, blood sinusoid lacunae with neutrophil infiltration, and phagocytosed bacteria in phagocyte cells were observed. Myocardial fiber hypertrophy and interstitial indistinction, nuclear matrices decreased in cardiac myocytes, and loose arrangement of myogenic fibers in myocardial cells were also observed. Angiectasia, capillary congestion, and tissue necrosis were found in the lung. No significant difference in histopathological and ultrastructural pathology in the parenchymal organ was observed between the 7.4×10⁵-7.4×10⁷ CFU/ml groups and the 7.4×10⁸-3.0×10¹¹ CFU/ml groups, and no specific death caused by Y. pestis infection was apparent in the 7.4×10⁵-7.4×10⁷ CFU/ml groups. Conclusion Y. pestis infection altered tissue and ultrastructural pathology in the parenchyma apparatus of great gerbils. In particular, the liver and spleen appeared to be the primary site of Y. pestis infection in great gerbils.