Abstract： Objective To explore the effects and significance of acetazolamide on the expression of aquaporin-4(AQP4) of gastric mucosal in rats with endotoxemia. Methods 30 SD rats were randomly divided into 3 groups: Sham operated control group( Control group) ,endotoxemia group( EDT group) and acetazolamide group( ATL group).The immunohistochemistry was used to assess the expression of the AQP4 in the gastric mucosal tissues. The serum tumor necrosis factor-α(TNF-α) and interleukin-1 β(IL-1β) levels in each group were measured by radioimmunoassay. Results The expression of AQP4 and the levels of serum TNF-αt and IL-1 ββ in EDT group were higher than those in control group( P ＜ 0.01 ). After the ALT treatment, the expression of AQP4 and the levels of serum TNF-α and IL1 β in ALT group were lower than those in EDT group( all P ＜0.01 ) and the expression of AQP4 in the gastric mucosal tissues in ALT group was also lower than those in EDT group( P ＜0.01 ). Conclusion The raising of AQP4 expression and increasing of serum TNF-α, IL-1β take part in the progress of gastric mucosal injury in rats with endotoxemia. ALT could protect the gastric mucosal tissues by lowering the AQP4 expression and reducing the levels of serum TNF-α and IL-l β.