Aim To investigate the correlation of matrix metalloproteinase-9 （MMP-9） levels and MMP-9-1562C＞T polymorphism with acute ischemic stroke （IS） and its “Trial of Org 10172 in Acute Stroke Treatment” （TOAST） subtypes in Uygur nationality. Methods A total of 284 patients with acute IS were enrolled using the method of case-control study, based on the standard of new TOAST classification, 91 patients were atherothrombosis （AT）, 150 patients were small artery disease （SAD） and 43 patients were cardioembolism （CE）. Meanwhiie, 226 age-and sex-matched physically healthy subjects were used as control group. The levels of serum MMP-9 and-1562C＞T gene polymorphism in each group were measured and analyzed by enzyme-linked immunosorbent assay and restriction fragment length polymorphism. Results The serum MMP-9 level in the IS group was sigrfificantly higher than that in the control group （0.308±0.033 mg/L vs 0.087±0.011 mg/L, t＝7.813, P＝0.000）. The serum MMP-9 level in the AT group and CE group were significantly higher than those in the groups of SAD （0.350±0.030 mg/L vs 0.261±0.029 mg/L, t＝4.156, P＝0.001 0.317±0.043 mg/L vs 0.261±0.029 mg/L, t＝2.877, P＝0.031）. Multivariate Logistic regression analysis showed that the increased serum MMP-9 level was an independent risk factor for ischemic stroke （OR: 1.012, 95% CI: 1.007～1.016, P<0.001）. There was no significant difference in the frequencies of genotype （χ²＝3.558, P＝0.058） and allele （χ²＝3.567, P＝0.059） of MMP-9-1562C＞T between the IS group and the control group. However, there were significant difference in the frequencies of genotype （χ²＝5.097, P＝0.024） and allele （χ²＝5.439, P＝0.02） of MMP-9-1562C＞T between the AT group and the control group. The CT＋TT genotype frequency in the AT group was significantly higher than the control group （24.2% vs 13.7%）. Multivariate Logistic regression analysis showed that MMP-9-1562C＞T polymomhism was not an independent risk factor for the IS group （OR: 0.821, 95% CI: 0.622～1.059, P＝0.124）, but it was an independent risk factor for the AT group （OR: 1.768, 95% CI: 1.178～2.677, P＝0.007）. Conclusions The serum MMP-9 level increased in Uygur patients with IS, especially in the patients with AT.