Abstract: Background and Objectives: Microcystin-LR has a toxic effect on several organs causing the destruction and fibrosis of these organs. This study was done to evaluate the antioxidant activity of silymarin on some oxidative stress parameters on heart and lung injuries induced by microcystin-LR in mice. Materials and Methods: Total 72 Balb/c male mice aged between five to seven weeks were grouped into 6; Group 1 contained twelve mice which were assigned as the healthy control group (C). Two microcystin-LR control groups assigned M6 and M12 contain 12 mice each. A fourth group contains twelve mice called the silymarin control group(S). The fifth and sixth groups contain twenty-four mice assigned as microcystin-LR silymarin groups SM6 and SM12. A blood sample was collected for estimation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The homogenates of heart and lungs were extracted for estimation of protein carbonyl content (CC), lipid peroxidation products (LPO), reduced glutathione (GSH), methylglyoxal (MG) and activity of protein phosphatase I (PPI). Results: Significant statistical differences in both ALT and AST were observed between all groups (P>0.01). In cardiac homogenate, a significant statistical difference was observed in PPI, LPO and CC between all groups (P<0.05). Furthermore, methylglyoxal showed a significant statistical difference between all groups (p<0.01). Conclusion: The findings suggested a potential therapeutic role of using silymarin as an antioxidant agent against cardiac and pulmonary injuries induced by MC-LR.