The present study is arranged to investigate the role of milk thistle (Silybum marianum) oil to improve the histological alterations as well as the deposition of collagen fibres, and the expression of the desmin by IHC against cardiac muscle induced experimentally in mice (Mus musculus) by CCl4. Sixty adult male albino mice were used and divided into six groups (n=10/each) ; GI: normal group received standard diet and free access to water without any treatment for one week; GΙΙ: control group, each mouse administered with M.T.O daily at a dose 1 ml/kg/bw/d orally for 4 weeks; GIII & GIV: mice injected intraperitoneally (i.p.) with 1 :1 (v/v) mixture of CCl4 and olive oil (1 ml/kg/bw) twice weekly for 4 & 6 weeks. GV & GVI: mice treated with CCl4 as in GIII & GIV then administered with M.T.O as in GII. Histological results of the cardiac muscle sections of normal and control mice groups (GI & GII) showed typical myocardial architecture with exposed normal distribution of delicate collagen fibers in the endomysium between the muscle fibers and around the blood vessels (by using Masson's trichrome dye). Cardiac muscles of CCl4-intoxicated mice groups (GIII& GIV) revealed a loss of cardiac muscle architecture and expressed excess deposition of collagen fibers in the endomysium of cardiomyofibers and around the blood vessels that increase with time. Mice treated with CCl4 then administered with M.T.O in GV& GVI. showed an obvious improvement in myocardial cells, where most of the muscle fibers looked normal with intact oval nuclei and reduction of the inflammatory leukocytes as well as thE reduction in the distribution of collagen fibers which appeared similar to the control ones. Immunostain against desmin expressed the cardiac muscle fibers of the ordinary mice groups (GI&GII) as a normal moderate to strong immunopositive reaction in the intercalated discs and Z lines. The intensity of the immunoreactivity to desmin was almost diminished in cardiomyocytes of CCl4 mice group for 4 & 6 weeks (GIII and GIV due to the disappearance of intercalated discs and Z lines in most cardiomyocytes. The mice groups took M.T.O (GIV and GVI) illustrated a marked recovery of desmin in the intercalated discs and Z lines and expressed approximately similar to the normal one. In conclusion, M.T.O has a beneficial role in the amelioration of mice's cardiac muscle disorders induced by CCl4 The current results promise to overcome cardiac disorders in human by M.T.O as a natural plant product.