Aims: As a metabolic disorder, the diabetes increases the oxidative stress, while it reduces the anti-oxidant defense system. The aim of the study was to determine the effects of the methanol extract of Silybum marianum on the glucose level, the oxidative indices, and the biochemical factors in the diabetic rats. Materials & Methods: In the experimental study, 24 male and white Wistar rats were studied. The rats were randomly divided into four 6-rat groups including healthy control (negative control), diabetic control without any extract treatment (positive control), and two diabetic groups treating by 150 and 100mg/kg methanol extract respectively. The diabetes was induced by 60mg/kg one-dose streptozotocin as intra-peritoneal injection. The diabetes symptoms having been observed, 4-week and daily extract treatment was done as intra-peritoneal injection. Data was analyzed using one-way ANOVA and the repeated measurement tests. Findings: The treatment, done by the methanol extract of the seeds of Silybum marianum, reduced weight, the blood glucose level, cholesterol, malondialdehyde, and protein carbonyl, while it increased HDL and the activity level of paraoxonase enzyme, in the treatment groups compared to diabetic control group. In addition, the most effective extract concentration, reducing cholesterol, glucose, protein carbonyl, malondialdehyde and increasing the activity level of paraoxonase enzyme, was 150mg/kg. And the most effective concentration, increasing HDL and weight, was 100mg/kg (p<0.05). Conclusion: The injection of methanol extract of the seeds of Silybum marianum positively changes the oxidative indices, as well as the biochemical factors, in the diabetic rats.