Background: Researches on attenuated Toxoplasma gondii vaccine have shown its protective effect against challenged infection in addition to its therapeutic rather than preventative activity against some autoimmune and malignant diseases. Rise in oxidative stress is one of the most common signs of toxoplasmosis; hence this study aims to determine local oxidative stress on hepatocytes as well as associated immune variations in mice vaccinated with gamma radiation-attenuated Toxoplasma gondii. Materials and Methods: Thirty female Swiss albino mice are divided into: normal control; mice infected with T. gondii cysts (infected control) and mice vaccinated with the same infective dose attenuated with 0.4 KGy of gamma radiation (vaccinated group). Results: Hepatic superoxide dismutase (SOD), Malondialdehyde (MDA) and inducible nitric oxidase (INOs) levels were significantly increased with a significant decrease in reduced glutathione (GSH) in liver tissues of infected control mice. Besides, serum levels of interlekin-10 (IL-10) and tumor necrosis factor-α (TNF-α) were significantly elevated. Moreover, histopathological examinations revealed distinct alterations with decreased nuclear expression of DNA in hepatocytes. Conversely, vaccinated group exhibited an improvement in oxidative stress and elevation in nuclear expression of DNA in hepatocytes collimated with an amelioration of the histopathological alterations. Furthermore, reduced serum IL-10 and TNF-α level were detected. Conclusion: It is concluded that attenuation of Toxoplasma gondii with gamma radiation exerted protective effect in liver tissues against oxidative stress and DNA damages of hepatocytes with an improvement of host´s immune response.