Objective To explore the clinical efficacy of Ebastine or Ebastine combined with Loratadine in the treatment of chronic refractory urticaria and influence on levels of peripheral blood interleukin-4 (IL-4), interferon-γ (IFN-γ) and immunoglobulin E (IgE).Methods 195 patients with chronic refractory urticaria treated in the hospital from October 2021 to October 2023 were selected as the research subjects, and were divided into 98 cases in control group and 97 cases in study group according to the random number table method. The control group was treated with Ebastine and the study group was given Ebastine combined with Loratadine. The symptoms and signs ［Four-Item Itch Questionnaire (FIIQ), Level Four Score (LFS) of wheal, maximum wheal size］ and levels of immune indicators (IL-4, IFN-γ, IgE) were recorded in the two groups before treatment and after 4 weeks of treatment. The quality of life scores ［Urticaria Activity Score (UAS), Chronic Urticaria Quality Of Life Score (CU-Q2oL)］ of the two groups of patients were compared before treatment and at 6 months after treatment, and the adverse drug reactions and recurrence within 6 months after treatment were statistically analyzed. Results After 4 weeks of treatment, the symptoms and signs (FIIQ, LFS, maximum wheal size) and partial immune indicators (IL-4, IgE) of the two groups were significantly lower than those before treatment, and the above indicators of study group were lower than those of control group (all P<0.05). The IFN-γ level was significantly higher than that before treatment, and the level was higher in study group than that in control group (all P<0.05). After 6 months of treatment, the quality of life scores (UAS, CU-Q2oL) were significantly lower in the two groups than those before treatment, and the scores of study group were lower compared with those of control group (all P<0.05). Adverse reactions in study group were significantly more than those in control group (P<0.05), and there was no statistical significance in the recurrence rate between the two groups within 6 months after treatment (P>0.05). Conclusion The application of Ebastine combined with Loratadine can effectively improve the symptoms and signs and recurrence and enhance the immune status and prognosis quality of life of patients with chronic refractory urticaria, therefore it is worthy of clinical application