Genistein is a major isoflavone with antioxidant and anti-inflammatory activities and hydrophobic features. To increase its bioavailability, researchers supplemented genistein with dietary oils. The present study aims to compare the effectiveness of genistein supplementation with water solution or oils and find the best possible dietary oil for fortification. A total of 135 male Sprague-Dawley rats were randomly assigned to nine groups, including one control group and eight acetic acid-induced colitis groups. The rats in the intervention groups were treated with 5 ml per kg body weight of oral pure and genistein fortified forms of extra virgin olive oil (EVOO), canola oil (CaO), and rice bran oil (RBO); the Genistein group (G) received 100 mg per kg body weight of genistein in aqueous solution orally. The colitis and control groups did not receive any treatment. The levels of colonic MDA (malondialdehyde), MPO (myeloperoxidase) activity, and IL-1β (interleukin-1β) were evaluated and a stereological analysis of colonic tissues was performed. All of the dietary oils (EVOO, CaO, and RBO) were effective at ameliorating the rats' oxidative and inflammatory status (p < 0.05); however, EVOO (with or without genistein) prescription resulted in slightly better results, especially with regard to the inflammatory profile. Additionally, delivering genistein via an oil vehicle was more efficient at reducing MDA formation, MPO activity, and IL-1β concentration than genistein in aqueous solution. The quantitative analysis of colonic tissue was consistent with the biochemical analysis. Our findings suggest that the oral administration of EVOO, canola oil, and rice bran oil can attenuate the elevated IL-1β levels and oxidative damage in induced colitis. Moreover, genistein fortified oils, especially EVOO, showed more beneficial effects in decreasing these markers in comparison with the pure oils or genistein (aqueous solution).