Background Matrix metalloproteinase-9 (MMP-9) is an enzyme that contributes to inflammation and tissue remodelling. In chronic urticaria, increased plasma levels of MMP-9 and its correlation with disease severity have been shown in several studies, suggesting that MMP-9 could be used to evaluate the effects of new treatments. We aimed to compare MMP-9 levels in chronic urticaria patients with those of healthy patients. Then we planned to investigate the changes in plasma MMP-9 levels with chronic urticaria treatment, the role of this enzyme in demonstrating the efficacy of treatment, and its correlation with C-reactive protein (CRP). Methods Forty-one patients with chronic urticaria who were scheduled for omalizumab treatment and 41 sex- and age-matched healthy volunteers were included in the study. In the patient group, before treatment and at the end of the 12th week, the urticaria activity score used for 7 consecutive days (UAS7) was calculated, and the MMP-9 and CRP levels were measured. Plasma MMP-9 levels were measured from venous blood in the control group. Results The plasma MMP-9 levels of the patients before treatment were significantly higher than those of the control group (P < .01). In the patient group, there was no significant relationship between the UAS7 score and the MMP-9 and CRP levels before treatment. The UAS7 values were 28 +/- 7 before omalizumab treatment and 5 +/- 6 at the end of the 12th week (P < .0001). The post-treatment MMP-9 levels (1818 +/- 297 pg/mL) were higher compared with the pre-treatment values (1617 +/- 380) (P < .05). The post-treatment CRP levels of the patients (2.41 +/- 2.17 mg/L) were lower than their pre-treatment CRP levels (8.20 +/- 19.70) (P < .05). Conclusion MMP-9 levels were not associated with the severity of disease, and MMP-9 levels were not decreased with treatment response. Therefore, MMP-9 cannot be used as a parameter of disease activity in chronic urticaria or to evaluate the efficacy of new treatments.