In this study, we evaluated homeostatic and functional disorders of the spleen in mice inoculated with Toxoplasma gondii. The kinetics of megakaryocyte and leukocyte production, body and spleen mass and certain histopathological aspects were analyzed. There was increased (P < 0.05) the accumulation of lipofuscin in the red pulp of the spleen, in the periods of 30 and 60 dpi of the infection, that is, in the chronification stage of the disease and decrease of the white pulp area. In addition, we observed (from 7dpi) a quantitative and qualitative increase (P < 0.05) in the deposition of collagen fibers in the spleen of all infected mice. Since resolution of the inflammatory process resulted in pathophysiological changes, we can suggest that the T. gondii invaded and multiplied in the cells of the white and red pulps of the spleen. Although we did not find the parasite in the spleen, this hypothesis is supported by the presence of diffuse inflammatory infiltrate, which extended through the spleen parenchyma of all inoculated mice. Taken together, our results suggest that T. gondii causes severe homeostatic disorders that have altered spleen physiology, including diffuse parenchymal inflammation, lipofuscinosis in histiocytes, early aging, collagenopathy, systemic sclerosis and spleen and white pulp atrophy.