Breast cancer is the most common cancer among women in the world and the incidence is increasing alarmingly. It was aimed to determine the effect of raloxifene (RAL) and fluoxetine (FLX) on selected parameters in 7,12âdimethylbenz(a)anthracene (DMBA)âinduced mammary carcinoma. Thirtyâtwo female Wistar albino rats were assorted into four groups: DMBA (group I), DMBA+RAL (group II), DMBA+FLX (group III), and DMBA+RAL+FLX (group IV). Mammary tissue vascular endothelial growth factor (VEGF), macrophage colonyâstimulating factor (MâCSF), matrix metalloproteinaseâ9 (MMPâ9), and tissue inhibitors of matrix metalloproteinaseâ1 (TIMPâ1) levels were determined by the enzymeâlinked immunosorbent assay method. The tissue VEGF levels were lower in group IV compared with DMBA group. Decreased MâCSF levels were observed in all therapeutic groups rather than the DMBA group, but the most effective decrease was found in group IV. Compared with the DMBA group, MMPâ9 levels were statistically significantly decreased in group II and group IV. However, TIMPâ1 levels were higher in the whole therapeutic groups rather than the DMBA group and the most effective increase was observed in group IV. Results of the present study suggest that combined therapy of RAL with FLX might lead to a better outcome targeting breast tumor.