Campylobacter jejuni (C. jejuni) is one of the leading causes of food-borne disease in the world with chickens being a major reservoir. A chicken whole genome 44K Agilent microarray was used to profile cecal gene expression with C. jejuni challenge. Day-old chicks from two genetically distinct broiler lines, previously characterized as resistant or susceptible to C. jejuni infection were orally inoculated with either mutant, wild-type (WT) C. jejuni or PBS. Ceca were harvested at 1 and 4 h post-inoculation (PI) to isolate total RNA. Eight biological replicates per group were used for pair comparison between infected and non-infected birds at each time point. The signal intensity for each gene was normalized and data reported on the log2 scale. A mixed model including line, treatment, time-point, array, dye, and all two-way interactions among them were used to identify differentially expressed genes (P<0.01). Within the resistant line, there were 2594 and 1129 differentially expressed genes in the mutant-infected and WT-infected groups when compared to the uninfected controls at 1 hour PI, and 833 and 1077 genes at 4 hours PI, respectively. Within the susceptible line, there were 604 and 397genes significantly expressed in the mutant-infected and WT-infected groups at 1 hour PI, and 2267 and 871 genes at 4 hours PI, respectively, when compared to the uninfected controls. The results suggest the resistant line initiates strong host gene expression early while the susceptible line showed a strong late host response. Moreover, mutant strain elicited more host response than wild-type strain in cecum.