Objective: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease in which the sinus and nasal mucosa are affected. We investigated the relationship between the genetic polymorphism of MMP9 (rs17576) and TIMP1 (rs48498) and serum levels, and we wanted to investigate the effect of MMP9 and TIMP1 genotypes on Vitamin serum levels in CRSwNP with and without Aspirin-Exacerbated Respiratory Disease (AERD). Materials and Methods: This study consisted of 99 patients with CRSwNP with AERD and CRSwNP without AERD. The RT-PCR method and ELISA were used in this study. ELISA was used for MMP9 and TIMP1 serum levels and Vitamin D levels. Results: Serum levels of MMP9 were markedly higher in AG genotype than GG genotype in CRSwNP with AERD. Serum levels of MMP9 were statistically higher in carrying of A (+) allele in CRSwNP with AERD than in not carrying of A (+) allele. In addition, serum levels of Vitamin D were discovered significantly lower in TIMP1 CT genotype in comparison to CC and TT genotypes in all of CRSwNP. Conclusion: The rising of MMP9 serum levels may be a marker of chronic inflammation or they may be a significant factor in the resistance to diseases. This study may lead to a further understanding of disease severity in CRSwNP with AERD.