Background and study aim: Iron has a critical part in several biological activities. Maintaining an optimal iron balance becomes especially important in the case of Toxoplasma gondii. This study aimed to assess the effects of iron and iron chelator, deferoxamine on toxoplasmosis outcome in the experimental mice utilizing histopathological and immuno- histochemical assessment of IL-6 and TGF- β levels expression in liver tissue.Patients and Methods: Sixty Swiss albino male mice were divided up into four equal groups as follows: (GI): control negative non-infected non-treated group; (GII): control positive, infected non- treated group; (GIII): infected iron supplemented group; (GIV): infected deferoxamine treated group.Results: Our data indicated that infected group (GII) showed marked histopathological changes represented byportal biliary reaction and lymphocytic cholangitis. The infected iron- supplemented group (GIII) exhibited marked histopathological changes of focal hepatocellular degeneration, scattered necrosis and apoptosis in liver tissues of experimentally infected mice that were greatly improved in GIV after chelation of iron using deferoxamine treatment. These findings were confirmed by immuno- histochemical assessment to investigate the expression of Il-6 which was highly expressed in GIII; 46.29 ± 13.89, but its expression was low in GIV; 10.49 ± 3.04 (p <0.001). Conversely, the highest expression of TGF-β was in GIV; 49.18 ±12.3 and its expression was low in GIII;12.45 ± 3.61 (p <0.001).Conclusion: Our findings suggest that deferoxamine can be a promising treatment for acute Toxoplasma (T.) gondii infection due to the limited availability of iron.