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Background and Aim: Diabetes mellitus causes enhanced oxidative stress due to increased production of oxygen free radicals and decreased activity of antioxidant defense system. Flavonolignan Silymarin has an antidiabetic effect. This study was conducted to evaluate the effect of its chronic administration on serum levels of aspartate and alanine aminotranferase and the heart and liver level of malondialdehyde. Materials and Methods: In this experimental study, 40 male Wistar rats were divided into 5 equal groups, i.e. control, Silymarin -treated control (100 mg/kg), diabetic, and two Silymarin- treated diabetic groups (50 and 100 mg/kg). Silymarin was daily administered (i.p.) to each of the group members ten days after streptozotocin injection for 4 weeks. Serum levels of aspartate and alanine aminotranferase were measured both before and at the end of the study. In addition, level of malondialdehyde (MDA) was measured in the liver and the heart tissues on the basis of the reaction of thiobarbituric acid. Results: Serum glucose level in high dose Silymarin-treated diabetic group was significantly lower as compared to diabetics in the sixth week (P=0.007).Moreover, diabetic rats showed a significant increase in their aspartate serum level (P=0.028) and alanine aminotranferase (P=0.008) and Silymarin treatment only significantly reduced serum level of alanine aminotranferase (P=0.034). In addition, diabetes was followed by increased level of MDA in the liver (P=0.008) and the heart (P=0.009) tissues and high-dose Silymarin treatment significantly reduced MDA level only in the liver tissues (P=0.026). Conclusion: Long-term treatment with silymarin at a dose of 100 mg/kg can attenuate serum level of alanine aminotranferase and hepatic MDA level and does not have any significant effects on serum level of aspartate aminotranferase and cardiac tissue level of MDA in the administered doses