Objective: I ) To evaluate whether neutralization therapy with weak acid is effective in reducing observed histopathologic esophageal tissue injury secondary to liquid alkali. 2 ) to quantify the temperature change of the neutralizing agent. and 3 ) to determine the effect of interval t o therapy on injury severity.Methods: Harvested Sprague-Dawley rat esophagi were catheterized and placed in an oxygenated saline bath (37°C) for 60 minutes and then fixed in 10% formalin. Nine groups ( t i = 10) were perfused with 50% sodium hydroxide (NaOH). Six of the groups were treated hy neutralization with cooled orange juice (OJ) or cola that was maintained between 2'C and 4°C. This was performed at 0, 5. or 30 minutes after injury. In addition, two positive control groups were exposed to OJ or cola at time 0 and were not exposed to strong alkali. A third control group was exposed to strong alkali hut was not administered any subsequent treatment. The temperature of the neutralizing agent was recorded prior to instillation and after exiting the esophagus. Blinded pathologic scoring of 0 (no injury) to 3 (severe) was performed for six histopathologic categories: epithelial cell viability, cornified epithelial cell differentiation, granular cell differentiation. epithelial cell nuclei, muscle cells, and muscle cell nuclei. Comparisons were made among treatment times using the Kruskal-Wallis test and linear trend analysis. Results:For each histopathologic category and each treatment mode, the Kruskal-Wallis test showed significant differences between the groups (p < 0.003) over time. Trend analyses showed more severe injury with delayed ncutralization therapy ( p < 0.05) for each treatment mode and histopathologic category. Conclusion:Early neutralization therapy with OJ or cola reduces acute esophageal alkali injury. Additional in-vivo study is needed before neutralization therapy is adopted for clinical use.