The swine leukocyte antigen (SLA)-DRA locus is noteworthy among other SLA class II loci for its limited variation and has not been investigated in depth. This study was investigated to detect polymorphisms of four exons of SLA-DRA gene and its association with piglet diarrhea in Landrace, Large White and Duroc pigs. No polymorphisms were detected in exon 3, while 2 SNPs (c.178G>A and c.211T>C), 2 SNPs (c.3093A>C and c.3104C>T) and 5 SNPs (c.4167A>G, c.4184A>G, c.4194A>G, c.4246A>G and c.4293G>A) were detected in exon 1, exon 2 and exon 4 respectively, and 1 SNP (c.4081T>C) in intron 3. Statistical results showed that genotype had significant effect on piglet diarrhea, individuals with genotype BC had a higher diarrhea score when compared with the genotypes AA, AB, AC and CC. Futhermore, genotype AC had a higher diarrhea score than the genotype CC in exon 1 (p<0.05); diarrhea scores of genotype AA and BB were higher than those of genotypes AC and CC in exon 2 (p<0.05); individuals with genotype AA had a higher diarrhea score than individuals with genotype AB and BB in exon 4 (p<0.05). Fourteen common haplotypes were founded by haplotype constructing of all SNPs in the three exons, its association with piglet diarrhea appeared that Hap2, 5, 8, 10, and 14 may be the susceptible haplotypes and Hap9 may be the resistant haplotype to piglet diarrhea. The genetic variations identified of the SLA-DRA gene may potentially be functional mutations related to piglet diarrhea.