This study aimed to explore the effects of modified Wendan Decoction combined with acupuncture on serum inflammatory markers and immune function in patients suffering from urticaria. A total of 150 urticaria patients admitted to our hospital were randomly assigned to two groups: the observation group (n = 75) and the control group (n = 75). The control group received levocetirizine tablets, while the observation group was treated with modified Wendan Decoction along with acupuncture. Following treatment, the observation group demonstrated a higher clinical efficacy compared to the control group, with a statistically significant difference (P < 0.05). Both groups experienced reductions in symptom scores, including erythema, burning sensation, pruritus, wheals, fever accompanied by epigastric pain, nausea and vomiting, fatigue, and poor appetite. However, the observation group showed significantly lower symptom scores than the control group (P < 0.05). Additionally, levels of IL-4, IL-10, IL-25, IL-33, and IFN-γ decreased in both groups after treatment, but the observation group exhibited lower levels than the control group, again with a statistically significant difference (P < 0.05). The recurrence rate was notably lower in the observation group compared to the control group (P < 0.05). The combination of modified Wendan Decoction and acupuncture effectively reduces serum inflammatory markers and enhances immune function in patients with urticaria. This treatment demonstrates significant clinical effectiveness and holds potential for broader application in clinical settings.© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.