In the present work we established a rapid, cost-effective and high-throughput method for genotyping using a multiplexed microsphere-based suspension array platform - Luminex xMAP which enabled us to analyze 3 SNPs in the MBL2 gene promoter and 5' UTR, and 3 coding SNPs exon 1 haplotypes, associated with different levels of MBL2 expression. Using this system MBL2 diversity in four different ethnic groups, namely, Asian (Japanese), Caucasian, Hispanic and African-American-assessed. Results showed significant variability in terms of allele, genotype, and haplotype distribution. Characteristic MBL haplotype patterns were defined for each ethnic group. A prevalence of haplotypes coding functional proteins capable of complement activation and pathogen opsonization was observed. Regardless of the significant diversity of individual haplotypes, a high, almost similar (25-28%) proportion of haplotypes associated with MBL deficiency was found in the four ethic groups. The proportion of individuals homozygous for the haplotypes resulting in complete MBL2 deficiency was also significant (2-10%). Considering the role of MBL2 in innate immunity and as a clinically relevant marker, the genotyping approach developed and the knowledge of the genetic variation in different ethnic groups will be relevant to future medical genetic studies.