Abstract: HLA is the most polymorphic gene family in human genome, which is imperative for human to face numerous heterogeneous bio-molecules. Previous studies on the formation of HLA polymorphism have been focused on gene cross-over. Here, we investigated the contribution of gene conversion, which is an important mechanism to generate polymor-phism at shaping different patterns of HLA-DRB genes. Analysis of all known HLA-DRB haplotypes and alleles demon-strated that this was a highly polymorphic gene family. Using Ester Betran’s algorithm, 32 gene conversion regions were identified. The minimal conversion tract was as short as 2 bp, and the maximum interval between two furthest SNPs was 204 bp. Moreover, gene conversion occurred more frequently in certain regions (71-75, 18-221) of various alleles, sug-gesting that these segments were conversion hotspots. Further analysis showed that the conversion regions of 71-75 and 205-217 appeared to correlate with populations of Oriental and Caucasian, respectively, indicating that conversion hotspots might be population specific.