Asthma is a common chronic inflammatory ailment affects the respiratory system leading to bronchial hyperreactivity. Both genetic and environmental factors play a principal role in asthma pathogenesis. Matrix Metalloproteinase-2 (MMP-2) encoded by MMP-2 gene and degrades type IV collagen leading to an inflammatory response. We assessed the serum level of MMP-2 in Egyptian asthmatic patients and also we investigated the association between the functional MMP-2 -1306 CNT promoter polymorphism and bronchial asthma susceptibility and finally we explored the effect of the polymorphism on the production of MMP-2 in asthmatic patients. This study was conducted on 80 stable asthmatic patients and 80 healthy age-matched individuals. SerumMMP- 2 and total IgE concentrations were measured by ELISA. Genomic DNA was extracted from whole blood and MMP-2 -1306 CNT polymorphism was genotyped by Real Time-PCR using TaqMan allele discrimination assay. Asthmatic patients had higher serum MMP-2 levels than controls. Subjects with the CT and TT genotypes had a decreased risk of asthma(OR=0.42, P=0.02, OR=0.12, P=0.04, respectively) in contrast to thosewith the CC genotype. A strong association was found between mutant T allele and protection against asthma (OR = 0.37, P = 0.002). Furthermore, serum levels of MMP-2 were significantly lower in asthmatic patients carrying CT and TT genotypes than those carrying CC genotypes. Bronchial asthma is associated with high serum levels of MMP-2, while MMP-2 -1306CNT gene polymorphism provides a significant protection against asthma manifestation through down-regulation ofMMP-2 gene expression leading to lower level of circulating MMP-2.