We conducted a study to investigate if lycopene could reduce gastrointestinal toxicity of abdominal and pelvic radiation in Wistar albino rats. Animals received either a control diet (Group 1), lycopene-supplemented diet (Group 2), control diet and radiation (Group 3), and lycopene-supplemented diet plus radiation (Group 4). In Groups 2 and 4, the rats received 5 mg/kg/day lycopene for 10 days. In Groups 3 and 4, the rats received single fraction 8 Gy abdominal and pelvic radiation (RT) on Day 10. Study endpoints included weight loss, diarrhea, duration of diarrhea, survival, and an oxidative stress marker, plasma level of thiobarbituric acid reactive substance (TBARS). The rats receiving RT only had significantly higher weight loss rate compared to the lycopene plus RT group (P = 0.001). Plasma TBARS levels after RT were also significantly higher in the RT only group compared to lycopene plus RT group (P = 0.001). In conclusion, lycopene supplementation significantly reduced the weight loss and prevented oxidative stress in rats treated with abdominopelvic radiation.