In our study, we found that fluorofenidone could inhibit the phosphorylation of the MAPK pathway, including P38, JNK, and ERK, and further suppressed the activation of the NF-κB pathway both in vivo and in vitro, which suggested that the beneficial effect of fluorofenidone in ALI may be attributed to the blocking of MAPK and NF-κB pathways. Here, MAPK8 is linked to acute respiratory distress syndrome.