Introduction and purpose The mechanism of omalizumab in urticaria is not literally known. Omalizumab may affect receptors on the mast cell surface in other ways, especially other than Fc epsilon RI. Materials and Methods Thirty patients who were treated with omalizumab with the diagnosis of chronic urticaria were included in the study. For serum vasoactive intestinal peptide (VIP), kallikrein (KAL), and substance p (SP) values, 5 mL of blood was taken from the patients. These bloods were centrifuged for 5 min and stored at -80 degrees until the levels were measured. The changes in values measured at baseline, third month, and sixth month were analyzed by Friedman test. A value of p < 0.05 was considered statistically significant results. Results While SP, KAL, and VIP values increased continuously, it was observed that the D-dimer value decreased. Conclusion This study shows that omalizumab can affect mast cells other than IgE. To the best of our knowledge, this is the first study to show the relationship between omalizumab and VIP.