n-3 Polyunsaturated fatty acids (PUFA) have a chemopreventive effect while n-6 PUFA promote carcinogenesis. The effect of these essential fatty acids may be related to oxidative stress. Therefore, the study was designed to evaluate the effect of different ratios of fish oil (FO) and corn oil (CO) in the prevention of colon cancer. Male Wistar rats were divided into control, dimethylhydrazine dihydrochloride (DMH) treated, FO + CO (1:1) and FO + CO (2.5:1). All the groups, except the control received a weekly injection of DMH for 4 weeks. The animals were sacrificed either 48 h later (initiation phase) or kept for 16 weeks (post initiation phase). DMH treatment in the initiation phase animals showed mild to moderate inflammation, decreased ROS and TrxR activity, increased antioxidants, apoptosis and ACF multiplicity. The post initiation study showed severe inflammation with hyperplasia, increased ACF multiplicity and ROS levels, a decrease in antioxidants and apoptosis. The FO + CO (1:1) treated animals showed severe inflammation, a decrease in ROS, an increase in antioxidants and apoptosis in the initiation phase. FO + CO (1:1) in the post initiation phase and FO + CO (2.5:1) in the initiation showed mild inflammation, increased ROS, apoptosis and decreased antioxidants. There was a decrease in ACF multiplicity and ROS levels, increased antioxidants and apoptosis in the post initiation phase study. The present study suggests that FO has a dose- and time-dependent chemopreventive effect in colon cancer mediated through oxidative stress and apoptosis.