The immunological characterization in the pathogenesis of urticaria, mainly regarding cytokine profile, needs more investigation. In this study, subgroups of the T, B and natural killer (NK) lymphocyte from peripheral blood and serum levels of interleukin (IL)-15, IL-21 and immunoglobulin (Ig)E were examined in patients with acute urticaria (AU) and chronic urticaria (CU). Moreover, symptom scores and course of the patients were assessed. The percentage of NK cells and the ratio of CD4(+)/CD8(+) increased, however, CD8(+) decreased in CU compared to controls (P < 0.01). But no significant changes of T, B and NK lymphocyte were found in AU. IL-15 and IL-21 significantly decreased in AU and CU, but IgE increased. CU with a positive autologous serum skin test were more likely to be associated with longer course and higher CD3(+), B cells and IL-21, and lower IgE (P < 0.01). Weak negative correlations were demonstrated between CD3(+), CD8(+) and scores in CU (r = -0.23, -0.25, P < 0.05). Significant correlations were found between B cells and scores and course in CU (r = 0.49, 0.65, P < 0.01). Moreover, a significant correlation was found between IL-21 and IgE (r = 0.42, P < 0.01) in CU. But no significant correlations were found in AU. Our findings supported the concept that both humoral immunity and cellular immunity dysregulation in the pathogenesis of urticaria - mainly related to the decrease of the serum levels of IL-15 and IL-21 - may induce the increasing expression of IgE produced by B cells.