Milk thistle ( Silybum marianum ) is a member of Asteraceae family and is known as a medicinal plant which is effective in treatment of liver disease. Due to climate and geographical conditions, Iran is extensive habitat of this plant. In order to design a breeding program, it is necessary to increace the knowledge genetic of variation and reproductive system of this plants. This study was conducted to evaluate the effect of reproductive system (self-pollination and cross pollination) on phenotypic traits, silymarin and oil of milk thistle genotypes under normal and drought stress conditions during 2014-2015 at the research farm of Isfahan University of Technology (IUT). For this purpose 22 genotypes resulted from self-pollination (S) along with 22 of corresponding genotypes which resulted from cross pollination (OP), were investigated as combined analysis (moisture environments) in randomized complete block design. Results showed that genotypes had high variation in terms of evaluated traits in both populations (S and OP). Overall mandatory selfing caused reduction in plant performance. Under drought stress environment, cross pollination caused the significant increase of seed yield and self-pollination increased thousand seed weight. Self-pollination increased thousand seed weight and decreased percentage of silymarin. The increase of thousand seed weight can be due to decrease of number of seed per capitol, which resulted from self-pollination. In this study, those genotypes which were related to stress maternal environment were superior in terms of percentage of oil and seed yield under both self and cross pollination. In general, genotype 7 (from Mahshahr) had the most average in terms of most traits under both self and cross pollination conditions. As, the negative effects of inbreeding were low in this genotype it can be used in the future breeding programs for developing inbred lines. Keywords : Silymarin- Reproductive system- Milk thistle- Morphological traits.