Thus, in previous studies, we have found that cytosine phosphodiester guanine oligodeoxynucleotide (CpG-ODN) is able to prevent mortality after challenge with a lethal dose of Escherichia coli up to 6 days post-CpG-ODN administration. Administration of CpG-ODN by the in-ovo route at day-18 of incubation would be the most favorable for large scale settings. However, since CpG-ODN is protective for 6 days’ post-administration, 3 days of protection would be lost during the hatching period and thus only the latter 3 days of protection would be for the newly hatched chick to use in its first week of life. In order to reap the full protective benefits of CpG-ODN, a method of delivery is needed at the day of hatch. Therefore, we have delivered CpG-ODN by the intrapulmonary (IPL) route and investigate the mechanisms of action.