ABSTRACT: Abstract Background: Exogenous 6-benzyladenine (6-BA) could improve leaf defense system activity. In order to better understand the regulation mechanism of exogenous 6-benzyladenine (6-BA) on waterlogged summer maize, three treatments including control (CK), waterlogging at the third leaf stage for 6 days (V3-6), and application of 100 mg dm-3 6-BA after waterlogging for 6 days (V3-6-B), were employed using summer maize hybrid DengHai 605 (DH605) as the experimental material. We used a labeling liquid chromatography-based quantitative proteomics approach with tandem mass tags to determine the changes in leaf protein abundance level at the tasseling stage. Results: Waterlogging significantly hindered plant growth and decreased the activities of SOD, POD and CAT. In addition, the activity of LOX was significantly increased after waterlogging. As a result, the content of MDA and H2O2 was significantly increased which incurred serious damages on cell membrane and cellular metabolism of summer maize. And, the leaf emergence rate, plant height and grain yield were significantly decreased by waterlogging. However, application of 6-BA effectively mitigated these adverse effects induced by waterlogging. Compared with V3-6, SOD, POD and CAT activity of V3-6-B were increased by 6.9%, 12.4%, and 18.5%, LOX were decreased by 13.6%. As a consequence, the contents of MDA and H2O2 in V3-6-B were decreased by 22.1% and 17.2%, respectively, compared to that of V3-6. In addition, the leaf emergence rate, plant height and grain yield were significantly increased by application of 6-BA. Based on proteomics profiling, the proteins involved in protein metabolism, ROS scavenging and fatty acid metabolism were significantly regulated by 6-BA, which suggested that application of 6-BA exaggerated the defensive response of summer maize at proteomic level. Conclusions: These results demonstrated that 6-BA had contrastive effects on waterlogged maize. By regulating key proteins related to ROS scavenging and fatty acid metabolism, 6-BA effectively increased the defense system activity of waterlogged summer maize, then balanced the protein metabolism and improved the plant physiological traits and grain yield.