Carrot Yellows (CY) is a devastating disease that has been a major constraint to carrot cultivation in many countries, causing significant yield losses. Candidatus Liberibacter solancearum (CLso) is the causative agent of CY and is transmitted by the carrot psyllid Bactericera trigonica. Management of diseases caused by Liberibacter species including CY, the citrus greening disease (Huanglongbing), and the Zebra Chip disease depends on chemical control for lowering the psyllid vector populations, leading to health, economic and environmental problems. Understanding the transmission of CLso by psyllids is fundamental to devising sustainable management strategies. Persistent transmission of vector-borne pathogens involves critical steps of adhesion, cell invasion, and replication inside the insect gut cells before passage to the hemolymph. Our previous studies have used microscopy and expression analyses and confirmed a role of the Endoplasmic Reticulum (ER) in inducing immune responses and subsequent molecular pathways that lead to programmed cell death (apoptosis) upon CLso infection in the insect gut. Key genes involved in ER stress-related pathways were found to be differentially regulated in CLso-infected psyllids. Feeding CLso-infected and uninfected psyllids with different ER stress agents resulted in significant regulation of PERK, one of the three sensors that activate the unfolded protein response (UPR). These results demonstrate that CLso actively regulates and manipulates gene expression in the insect gut during transmission and this site is a strong candidate for targeting and regulating the transmission.