Coccidiosis, a common poultry enteric disease typically characterized by intestinal lesions and reduced performance, is caused by Eimeria species. Lesions induced by Eimeria in Coccidiosis affected chickens was previously reported to be associated with the expression of the chicken liver expressed antimicrobial peptide-2 (chLEAP-2) gene, a component of the innate immune system. Here, we screened the chLEAP-2 gene for structural variations and evaluated the relationships among its haplotypes (based on haplogroups), expression levels and lesion score in Eimeria -challenged chickens. A total of 16 SNPs were detected within a region of 4.1 kb of chLEAP-2 gene, including 7 each in the promoter and introns. Two SNPs were identified in exon 2. One of these was a non-synonymous SNP, which changes amino acid from cysteine to tyrosine. Six of the 16 SNPs did not deviate from HWE (P>0.05) while remaining SNPs deviated from HWE (P<0.05). Strong LD existed among several SNPs which ranged from 0.53 to 0.84. A total of 6 haplogroups was derived from the SNPs with frequencies that ranged from 0.11 to 0.26. Gene expression among the haplogroups varied, though not significantly, with highest down-regulation observed in Hap6 and the lowest in Hap1. Differences among haplogroups for lesion score were not statistically significant (P>0.05), though birds in Hap6 appeared to have higher LS score. At a minimum, the data does not support an association between DNA variation in the chLEAP-2 gene and the chickens response to Eimeria maxima based on lesion score. However, these data provide a foundation that will facilitate future association and linkage studies between chLEAP-2 and other traits in the chicken using a candidate gene approach.