Xanthomonas　oryzae　severely　impacts　the　yield　and　quality　of　rice.　Antibiotics　are　the　most　common　control　measure　for　this　pathogen;　however,　the　overuse　of　antibiotics　in　past　decades　has　caused　bacterial　resistance　to　these　antibiotics.　The　agricultural　context　is　of　particular　importance　as　antibiotic-resistant　bacteria　are　prevalent,　but　the　resistance　mechanism　largely　remains　unexplored.　Herein,　using　gas　chromatography-mass　spectrometry　(GC-MS),　we　demonstrated　that　zhongshengmycin-resistant　X.　oryzae　(Xoo-Rzs)　and　zhongshengmycin-sensitive　X.　oryzae　(Xoo-S)　have　distinct　metabolic　profiles.　We　found　that　the　resistance　to　zhongshengmycin　(ZS)　in　X.　oryzae　is　related　to　increased　fatty　acid　biosynthesis.　This　was　demonstrated　by　measuring　the　Acetyl-CoA　carboxylase　(ACC)　activity,　the　expression　levels　of　enzyme　genes　involved　in　the　fatty　acid　biosynthesis　and　degradation　pathways,　and　adding　exogenous　materials,　i.e.,　triclosan　and　fatty　acids.　Our　work　provides　a　basis　for　the　subsequent　control　of　the　production　of　antibiotic-resistant　strains　of　X.　oryzae　and　the　development　of　coping　strategies.