Introduction Esophageal cancer consists of two distinct types –esophageal adenocarcinoma (EAC) and squamous cell carcinoma (SCC), both of which differ significantly in their etiology. Freeze dried black raspberry (BRB) has been consistent in its ability to modulate the biomarkers and reduce the incidence of carcinogen-induced SCC in rats. In our previous studies in the esophagoduodenal anastomosis (EDA) model, we have shown that the early modulation of Manganese Superoxide dismutase (MnSOD) significantly correlates with the development of reflux-induced EAC in rats. In this study we looked at the short-term effects of a BRB supplemented diet on the modulation of antioxidant enzymes in reflux-induced esophagitis. Methods Male SD rats (8 wo; n=3–5) were randomized into 3 groups- sham-operated, fed control AIN-93M diet (SH-CD), EDA operated and fed either control diet (EDA-CD) or 2.5% (w/w) BRB diet (EDA-BRB). The effect of both reflux and dietary supplementation was analyzed 2 and 4 weeks after EDA surgery. Results Animals in EDA groups had significantly lower weight gain and diet intake compared to SH-CD (p<0.05). The sham operated animals, received an average esophagitis score of 0.1 ± 0.1, this increased significantly in EDA –CD animals to 1.8 ± 0.14 (p< 0.001 vs SH-CD) and in EDA-BRB group to 1.7 ± 0.06 (p< 0.001 vs SH-CD), with BE changes also present. However, dietary supplementation of BRB did not alter or ameliorate the grade of esophagitis or the induction of BE. BRB diet caused a 43% increase in MnSOD levels compared to EDA-CD (0.73 ± 0.16; p=0.09), however, this effect was not statistically significant and at 4 weeks, EDA-CD (0.58 ±0.12) showed an increase in MnSOD expression compared to SH-CD (0.34 ± 0.01). Conclusions In conclusion, our data suggests that dietary BRB does not increase the levels of cellular antioxidant enzymes or reduce the levels of lipid peroxidation compared to a control diet, in a short-term study of gastroesophageal reflux induction in the EDA animal model. However, it remains to be tested whether this is indicative of its ineffectiveness to inhibit reflux-induced EAC incidence over long-term.