The high-mobility group A1 (HMGA1) gene has been previously identified as a potential novel candidate gene for susceptibility to insulin resistance and type 2 diabetes (T2D) mellitus. For this reason, several studies have been conducted in recent years examining the association of the HMGA1 gene variant rs146052672 (also designated IVS5-13insC) with T2D. Because of non-univocal data and non-overlapping results among laboratories, we conducted the current meta-analysis with the aim to yield a more precise and reliable conclusion for this association. Using predetermined inclusion criteria, MEDLINE, PubMed, Web of Science, Scopus, Google Scholar and Embase were searched for all relevant available literature published until November 2014. Two of the authors independently evaluated the quality of the included studies and extracted the data. Values from the single studies were combined to determine the meta-analysis pooled estimates. Heterogeneity and publication bias were also examined. Among the articles reviewed, five studies (for a total of 13,789 cases and 13,460 controls) met the predetermined criteria for inclusion in this meta-analysis. The combined adjusted odds ratio estimates revealed that the rs146052672 variant genotype had an overall statistically significant effect on increasing the risk of development of T2D. As most of the study subjects were Caucasian, further studies are needed to establish whether the association of this variant with an increased risk of T2D is generalizable to other populations. Also, in the light of this result, it would appear to be highly desirable that further in-depth investigations should be undertaken to elucidate the biological significance of the HMGA1 rs146052672 variant.