The leading cause of cancer-related death is colorectal cancer, and inflammatory bowel disease is a risk factor for this disease. Azoxymethane (AOM) is a potent cancer inducer widely used in rats for colon cancer. The current study was scrutinizing the chemo-protective effect of geraniin against AOM induced colorectal cancer via alteration of oxidative stress and inflammatory cytokines. The rats were divided into different groups such as Group I: normal control, Group II geraniin (20 mg/kg), Group III: received AOM, Group IV-VI: AOM + geraniin (5, 10 and 20 mg/kg), respectively. All group of rats were received treatment for 16 weeks. At the end of the experimental study, the hepatic, biochemical, phase II antioxidant, antioxidant enzymes, cytokines, apoptosis and inflammatory mediators were estimated. Geraniin treatment significantly reduced tumor weight and enhanced body weight. Geraniin administration also altered the level of antioxidant parameters-superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR); phase I enzymes - cytochrome B5, cytochrome P450; phase II enzymes - Glutathione-STransferase (GST), UDP-Glucuronyl transferase (UDP-GT) respectively. Obtained results also demonstrate that geraniin treatment reduced the level of pro-inflammatory cytokines such as IL-2, IL-1 alpha, IL-10, IL-113, IL-4, IL-6, IL-12, IL-17A, IFN-gamma, tumor necrosis factor-alpha, G-CSF, and GM-CSF. Geraniin also reduced the expression of IL-1 alpha, IL-113, IL-6, IFN-gamma, G-CSF, and GM-CSF. On the basis of result we can conclude that geraniin reduced the colorectal cancer via inflammatory pathway.