Gliotoxin (GT) is sulfur-containing mycotoxin within the 2,5-diketopiperazines class. First discovery from Gliocladium. Later discovered from different strains belonging to Aspergillus fumigatus mainly those have glicluster. This study outlines a study on the histological effects of gliotoxin (GT) on mouse brain and spleen tissues using light and electron microscopy, with a focus on its interaction with matrix metalloproteinases (MMPs). Histopathological changes through MMPs expressing variability estimated by using Immunohistochemistry (IHC). Mature mice were injected intraperitoneally with acute doses determined by data response analysis (EC50/IC50) as (125, 250, and 500 μg/ml) of GT and compared with a control group that received (methanol 10%). GT highlights specific histopathological changes, such as amyloid aggregation, apoptosis, and MMP expression. Evidence of infected spleen appears as Amyloid (insoluble protein) aggregates on red pulp, accumulation of phagocytic cells, and apoptosis of lymphocytes in white pulp. On the other hand, tissue vacuolation and atrophy of glial cells, necrosis of neuronal cells, and damage to Purkinje fibers on infected brains. IHC analysis showed MMP1 and MMP7 expression induction on mice spleen treated with different concentrations of GT. MMP-1 expression was induced 1.3 times when treated with 500 μg/ml compared with control, while the induction on MMP7 expression reached up to 3 times when treated with 500 μg/ml compared with control. Based on the information provided, it can be inferred that any harmful effects caused by toxins will impact and change the normal physiological expression of matrix metalloproteinases 1 & 7