Background: Beta-thalassemia major (β-TM) is a genetic hemoglobinopathy that necessitates frequent blood transfusions and is brought on by defective β-globin chain synthesis. The family of zinc-dependent endopeptidases known as matrix metalloproteinases (MMPs) is in charge of both pathological and physiological tissue remodelling. Aim of work: To detect plasma levels of matrix metalloproteinase 9 in beta thalassemia patients. Subjects and methods: This case control study was conducted in the pediatric hematology out-patient clinic of Zagazig university hospitals during the period from March 2019 till October 2019. The study included 50 patients more than 10 years of both sexes and with beta thalassemia during their regular follow up visits. 50 age and sex matched healthy children were also included as a control group. All patients were subjected to full medical history and thorough clinical examination. Routine investigations for beta thalassemia were done. Biochemical study of plasma matrix metalloproteinase 9 was also conducted by ELISA. Results: MMP-9 was significantly higher in patients than controls (112.5 versus 18.5 pg/ml), respectively. Regarding the relationship between serum level of MMP-9 and demographic characteristics of patients, though patients >15 years and females had higher levels of MMP-9 yet, the difference didn't reach a statistically significant level. MMP-9 levels were significantly higher in patients with complications than those without complications. Conclusion: We concluded that thalassemia major patients had considerably increased plasma MMP-9 levels. MMP-9 seems to be a valuable marker in those patients.