Cancer starts when cells in the body start to grow out of control (malignant growth). Colorectal cancer starts in the colon or the rectum. Annona Muricata is a medicinal plant and is considered as a basis for health preservation and care worldwide. Colorectal cancer has reached epidemic proportions and is considered as a serious health problem, therefore treatment and cure of this disease is of great clinical importance. 1,2 dimethylhydrazine (DMH) is a potent carcinogen for colon cancer in rats. In this study, rats were randomly allocated into six groups: control, extract alone, DMH, extract and DMH together, extract before DMH, DMH before extract. DMH was injected subcutaneously at 25mg/1000g body weight once a week for 16 weeks, while the ethanol extract of Annona muricata leaves (EEAML) were administered to rats orally at 120mg/1000g. After sacrifice, colon and liver sections were dissected out for histological and some biochemical analysis. Blood was also collected in EDTA bottles for hematological assays. The group injected with DMH (subcutaneously) and orally administered leaves extract of A. Muricata simultaneously showed similar results with the rats fed with normal feed, as there was absence of polyps in the rats’ colon when compared with those injected with DMH alone for 16 weeks. Malondialdehyde level of rats injected with DMH were significantly increased (p ˂ 0.05) compared to the control. Hematology indices and caspase 3 activity show the protective effects of EEAML against DMH.