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 crossover. Here, we investigated the contribution of gene conversion, which is an important mechanism to generate polymorphism at shaping different patterns of HLA-DRB genes. Analysis of all known HLA-DRB haplotypes and alleles demonstrated 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, suggesting 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.