Abstract: Objective To explore the therapeutic effect of oxymatrine on chronic urticaria and its immune mechanism. Methods Totally, 69 patients were randomly and equally divided into 3 groups to receive treatment with oral mizolastine alone （mizolastine group）, oral mizolastine and intramuscular oxymatrine （combination group）, intramuscular oxymatrine alone （oxymatrine group）, respectively. The dose of mizolastine and oxymatrine was 10 mg and 400 mg daily, respectively, and the treatment lasted 15 days. Efficacy was assessed according to pruritus intensity and number of erythema and wheals on day 7, 14, and 28 after the beginning of treatment. Venous blood was obtained from patients at the baseline, on day 14, 28 after the initiating of treatment and subjected to the detection of CD4+Foxp3+ regulatory T cell populations via three-color fluorescence flow cytometric analysis. Results The efficacy in combination and oxymatrine groups were significantly higher than that in mizolastine group （t = 49.18, P < 0.01）, while there was no statistical difference between the combination group and oxymatrine group （t = 0.529, P > 0.05）. The proportion of Foxp3+CD4+CD25+ regulatory T cells in peripheral blood was significantly increased in patients treated with oxymatrine, compared with normal human controls and patients treated with mizolastine （all P < 0.05）. Conclusions Oxymatrine has a marked effect on the treatment of chronic urticaria, likely by increasing the proportion of Foxp3+CD4+CD25+ regulatory T cells in peripheral blood of patients.