Background: Chronic urticaria (CU) is short-lived itching maculopapular skin lesions with or without angioedema for more than 6 weeks. Sixty percent of CU patients were classified as chronic idiopathic urticaria (CIU) with an underlying autoimmune mechanism. Objective: This study aims to evaluate the serum cytokine profiles of CIU and investigate the possible mechanism of autologous serum therapy (AST) for autologous serum skin test (ASST) positive CIU patients. Methods: In total 8 CIU patients, 6 were ASST positive and 4 of the 6 patients received AST for 9 weeks. All patients in study group are subjected to detect anti-nuclear antibodies and autoimmune thyroid disease. Anti-histamines were allowed to be consumed when needed during weekly serum therapy. Clinical symptoms and the serum cytokine levels including IL-4, IL-5, IL-9, IL-13, IL-17, IL-6, TNF-α, IL-12(p70), IL-17A and INF-γ were monitored and analyzed. Results: The CIU patients showed significantly increased IL-9 (6.29±4.29 versus 2.28±1.17 pg/ml) and IL-6 (6.16±5.58 versus 2.23±0.96 pg/ml) serum level compared to control group. CIU patients with positive ASST had higher IFN-γ compared to negative ASST. Furthermore, higher TNF-α and IFN-γ in ASST positive patients had better response to AST. In addition, IL-9 was the only cytokine that decreased gradually after AST. Conclusion: Based on our results, the cytokines IL-9, IL-6 and TNF-α are involved in mechanism of CIU inflammation. The IFN-α increase potentially leads to CIU patients with ASST positive; whereas higher level of TNF-α might be crucial for successful AST.