Acute lung injury (ALI) induced by intestinal ischemia/reperfusion (II/R) has high incidence and mortality, in which IL-1β was essential for the full development of ALI. However, the detailed regulating mechanism for this phenomenon remains to be unclear. The purpose of this study was to investigate whether inhibition of P38 MAPK could downregulate the expression of IL-1β to protect lung from acute injury in II/R rats. Here, we found that the level of pulmonary edema at 16 hours after operation (hpo) was obviously enhanced compared to that in 8hpo and sham groups. Immunofluorescent staining demonstrated that IL-1β and P38 MAPK were detected in lung tissues. And rats with II/R have the highest translation level for IL-1β and phosphorylation of P38 MAPK in lung tissues at 16hpo compared with 8hpo and sham groups. Moreover, administration of SB239063, an inhibitor of P38 α and β, could effectively downregulate the expressions of IL-1β and protects lung tissues from injury in II/R rats. Our findings indicate that the inhibition of P38 α and β may downregulate the expression of IL-1β to protect lung from acute injury in II/R, which could be used as a potential target for reducing ALI induced by II/R in the future clinical trial.