The pathogen-induced plant defense signaling network consists of multiple components, although only some of them are characterized. Most of the known components function either as activators or repressors in host-pathogen interactions. Here we report that a mitogen-activated protein kinase, OsMPK6, functions both as an activator and a repressor in rice resistance against Xanthomonas oryzae pv. oryzae (Xoo), the causal organism of bacterial blight disease. Activation of OsMPK6 resulted in the formation of lesion mimics and local resistance to Xoo, accompanied by the accumulation of salicylic acid (SA) and jasmonic acid (JA), and the induced expression of SA- and JA-signaling genes. Nuclear localization of OsMPK6 was essential for local resistance, suggesting that modulating the expression of defense-responsive genes through transcription regulators may be the primary mechanism of OsMPK6-mediated local resistance. The knock-out of OsMPK6 resulted in enhanced Xoo resistance, increased accumulation of SA and enhanced resistance to X. oryzae pv. oryzicola, the causal organism of bacterial streak disease, in systemic tissues. Xoo infection induced the expression of PR1a, the marker gene of systemic acquired resistance (SAR), in systemic health tissues of OsMPK6-knock-out plants. These results suggest that OsMPK6 negatively regulates SAR. Thus OsMPK6 is a two-faced player in the rice-Xoo interaction.