B-cell immunity participates in the pathogenesis of ulcerative colitis (UC). The immune balance between follicular regulatory T (TFR) cells and follicular helper T (TFH) cells is important in regulating B-cell responses. However, the alteration of TFR/TFH balance in UC remains unclear. Peripheral blood from 25 UC patients and 15 healthy controls was examined for the frequencies of circulating TFR, TFH, and regulatory T (Treg) cells by flow cytometry. Levels of serum cytokines were measured using cytometric bead array (CBA). Disease activity was evaluated by the Mayo Clinic Score. Compared with controls, UC patients ex- hibited significant reductions in circulating Foxp3(+)CXCR5(+) TFR cells, the subset interleukin (IL)-10(+)Foxp3(+)CXCR5(+) cells, and Treg cells, but significant expansions in Foxp3 CXCR5(+) TFH cells and IL-21 (+)Foxp3 CXCR5(+) cells. UC patients also had reduced levels of serum IL-10 and elevated levels of serum IL-21. The values of Mayo Clinic Score, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) in UC patients were negatively correlated with circulating TFR cells, serum IL-10 level, and TFR/TFH ratio, while positively correlated with circulating TFH cells and serum IL-21 level. Alterations in circulating TFR and TFH cells shift the balance from immune tolerance to immune responsive state, contributing to dysregulated B-cell immunity and the pathogenesis of UC.