Abstract : Breast cancer is a major threat worldwide, despite various therapeutic measures, it remains associated with high mortality rate. Argemone mexicana, traditionally used in several conditions, experimentally, plant extract showed anti-microbial, antioxidant, cytotoxic, and anti-cancer properties. However, there is lack of reports regarding its anticancer activity in-vivo. This study is aimed at investigating the anticancer properties of Argemone mexicana leaves (AML) extract on DMBA-induced mammary tumors. Female rats, 7-8 weeks old (100 ± 20 g) were used for the study and tumors were induced by DMBA (25 mg/kg/b.w/S.C). After the development of palpable nodule (10-12 weeks), the rats were treated with AML methanolic extract (200, 400 mg/kg b.w) and tamoxifen(TAM) at 10 mg/kg/b.w (standard drug) orally for 12 weeks. At the end of experiment, tumours were excised, measured weight and volume, then used for biochemical and histopathological studies. As a results, AML treatment showed significantly reduced mammary tumor weight and volume (P < 0.01), along with significant reduction (P < 0.0001) in tumour marker(CEA) and malondialdehyde (MDA) level. Significant (P < 0.0001) improvement in SOD, CAT, GSH levels were also observed after the treatment with AML extract. These effects contributed to the decrease the density of cancer cells in breast tumors, and the invasion of these cells into the tumor connective tissue. In conclusion, the extract of AML, contains anti-oxidants and anti-proliferative effects, it can be used as a therapeutic medicine against breast cancer.