Cancer is one of the diseases that cause the highest rate of morbidity and mortality in the world. And colorectal cancer as of know is ranked number 3 in the most prevalence cancer in Indonesia. Chemotherapy, radiotherapy, and surgery are still the main choice of cancer treatment. But, those therapy have various side effect, especially chemtherapy that have systemic response. Lunasin is one of the natural substance which mean less side effects, that have high anticancer effect by the inhibition of acetyl histone and from the suppression of NF-kB. This research aims to determine inhibitory potential of lunasin against the progression of the histopatological sign of colorectal cancer in rectum of mice induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) that acts as cancer inducer. 24 mice was injected with AOM and DSS intraperitoneal. Then it was divided into 4 different group; control group, group that was given 20mg/kg lunasin (low dose), group that was given 30mg/kg lunasin (medium dose), group that is given 40mg/kg lunasin (high dose). And then, the rectum specimen was taken. The histopatological sign observed are inflammation, hyperplasia, and angiogenesis. The result show that lunasin extract is proven to decrease the amount of angiogenesis, hyperplasia, and inflammation. But, in inflammation and hyperplasia significant reduction is only found after increasing the dose of lunasin extract for a minimum of 20mg/kg of mice body weight. For angiogensis, the signficcant reduction of angiogenesisn is only founded after giving the high dose lunasin (40mg/kg of mice body weight). In conclusion, lunasin is able to reduce the progression of colorectal cancer in rectum of mice induced by AOM and DSS.