Objective To explore the effect of montelukast sodium combined with olatadine in the treatment of chronic urticaria. Methods A total of 86 patients with chronic urticaria admitted to Hexi District Tianta Street Community Health Service Center of Tianjin from November 2020 to November 2023 were selected and divided into control group and study group according to different treatment schemes, with 43 patients in each group. The control group was given olopatadine alone, and the study group was given montelukast sodium combined with olopatadine. The therapeutic effect, clinical symptom score, cytokine level and quality of life score were compared between the two groups. Results The total effective rate of the study group was 95.35%, which was higher than 81.40% of the control group (P <0.05). The clinical symptom scores of the two groups after treatment were lower than those before treatment, and those in the study group was better than those in the control group (P <0.05). The levels of IL- 4, LT, IFN-γ and IgE in the two groups after treatment were better than those before treatment, and those in the study group were better than those in the control group (P <0.05). The scores of each dimension of DLQI in the two groups after treatment were lower than those before treatment, and those in the study group were lower than those in the control group (P <0.05). Conclusion During the treatment of chronic urticaria with olopatadine, the combined application of montelukast sodium can effectively alleviate the clinical symptoms of patients, regulate the level of immune inflammatory factors, improve the therapeutic effect. It is of positive significance to promote the rehabilitation and improve the quality of life.