Capsaicin, is commonly used in folk medicine to management oxidative stress in cells and might decrease the riskiness effects of cancers. The purpose of this study was to evaluate the suppressive activity of capsaicin against mammary carcinoma induced by N-nitrosomethylurea in rats. The study continued for 16 weeks. The sample consisted of 80 female rats which were divided equally into four groups and the following investigations were recorded: Body and gain weights, estradiol and progesterone, Carcinoembryonic Antigen, anti-oxidant enzymes, oxidative stress marker, histopathological and proliferating cell nuclear antigen immunohistochemical. N-nitrosomethylurea treated group displayed a significant decrease body weight and anti-oxidant enzymes. Also, subjects in this group displayed a significant increase estradiol, progesterone, CEA and Malondialdehyde. Additionally, the NMU exposure and capsaicin treated group significantly showed the protective potential of capsaicin in restoring the altered sexual hormones, antioxidants and other biochemical analyses. Rats treated with NMU and protected with capsaicin improved the histopathological changes induced by NMU and showed that the desquamation of most of the layers of carcinoma cells leaving one or two epithelial layers in some cases and in some instances. Animals treated with NMU immunostained for PCNA displayed the strong positive stained nuclei in most of the cells, but in capsaicin treated against the NMU effects immunostained for PCNA displayed that the positive stained nuclei was less than that detected in NMU group. To conclude, the results have clearly shown that capsaicin performs a very important defensive role during breast carcinogenesis and has the ability to act as a chemo-suppressive factor against NMU effects.