Endoplasmic reticulum (ER)-mediated protein secretion and quality control have been shown to play an important role in immune responses in both animals and plants. In mammals, the ER membrane-located IRE1 kinase/endoribonuclease, a key regulator of unfolded protein response (UPR), is required for plasma cell development to accommodate massive secretion of immunoglobulins. Plant cells can secrete the so-called pathogenesis-related (PR) proteins with antimicrobial activities upon pathogen challenge. However, whether IRE1 plays any role in plant immunity is not known. Arabidopsis thaliana has two copies of IRE1, IRE1a and IRE1b. Here, we show that both IRE1a and IRE1b are transcriptionally induced during chemically-induced ER stress, bacterial pathogen infection and treatment with the immune signal salicylic acid (SA). However, we found that IRE1a plays a predominant role in regulating secretion of PR proteins upon SA treatment. Consequently, the ire1a shows enhanced susceptibility to a bacterial pathogen and fails to establish effective systemic acquired resistance. This immune deficiency in ire1a is partly due to a defect in SA- and pathogen-triggered bZIP60 mRNA splicing, a transcription factor required for the regulation of UPR-responsive genes. Consistently, we demonstrated preferential requirements of IRE1a and IRE1b for bZIP60 splicing upon pathogen infection and tunicamycin-induced stress, respectively. We also show that SA-dependent induction of UPR-responsive genes is altered in the bzip60 mutant resulting in susceptibility to a bacterial pathogen. These results indicate that the IRE1/bZIP60 branch of UPR is a part of the plant response to pathogens for which the two Arabidopsis isoforms play only partially overlapping roles.