Objective To investigate the association between matrix metalloproteinase-12 (MMP-12) gene polymorphisms and ischemic stroke in patients with type 2 diabetes.Methods A total of 217 patients with type 2 diabetes complicated by ischemic stroke who were treated in our department from January 2013 to December 2015 were enrolled as case group, and according to the TOAST type, they were divided into large artery atherosclerosis (LAA) group (88 patients) and non-LAA group (n-LAA group, 129 patients). A total of 100 patients with type 2 diabetes who had no ischemic stroke and underwent physical examination in our hospital during the same period of time were enrolled as control group. Polymerase chain reaction-restriction fragment length polymorphism was used to measure the differences in MMP-12 (-82 A/G) and MMP-12 (-1082 A/G) gene polymorphisms between groups.Results There were no significant differences in the frequencies of MMP-12 (82 A/G) genotypes and alleles between the case group and the control group, as well as between the n-LAA group and the control group (P>0.05). Compared with the control group, the LAA group had significantly higher frequencies of (G/G+A/G) genotypes (22.73% vs 11.00%, P=0.031) and G allele (18.18% vs 10.05%, P=0.033). There were no significant differences in the frequencies of MMP-12 (-1082 A/G) genotypes and alleles between the n-LAA group and the control group (P>0.05). Compared with the control group, the case group and the LAA group had significantly higher frequencies of (G/G+A/G) genotypes (33.64%/37.50% vs 22.00%, P=0.036 and P=0.020) and G allele (25.58%/30.68% vs 17.00%, P=0.017 and P=0.002). The multivariate logistic regression analysis showed that G allele at MMP-12-82A/G (OR=1.107, 95% CI 1.010-1.371, P=0.031) and G allele at MMP-12-1082A/G (OR=1.285, 95% CI 1.142-1.817, P=0.010) were risk factors for the development of LAA in patients with type 2 diabetes.Conclusions For patients with type 2 diabetes, gene polymorphisms of G allele in MMP-12 (-82 A/G) and MMP-12 (-1082 A/G) may be closely associated with LAA.