Background Peanut (PN)-anaphylaxis is potentially life threatening. We previously reported that a Chinese herbal medicine preparation, food allergy herbal formula-2 (FAEF-2), prevented peanut allergy (PNA) in mice when administered during sensitization. Objective To investigate whether FAFIF-2 also can prevent anaphylactic reactions administered to mice with established PNA and, if so, whether protection would persist after cessation of therapy. Methods C3H/HeJ mice sensitized and boosted over 8 weeks with a standard protocol known to establish PN hypersensitivity received seven weeks of FAHF-2 treatment or water as a sham treatment. Mice were subsequently challenged with PN at week 14 (1-day post-therapy) and week 18 (4-week post-therapy) to evaluate the efficacy and persistence of FAEF-2 treatment by assessing anaphylactic scores, core body temperatures and plasma histamine levels. Serum PN-specific antibody levels and cytokine profiles from splenocytes and mesenteric lymph node (MLN) cells were also determined. Results All sham-treated mice challenged at weeks 14 and 18 showed anaphylactic symptoms. In contrast, FAEF-2-treated mice showed no sign of anaphylactic reactions. PN-specific IgE levels in FAHF-2-treated mice also were reduced whereas IgG2a levels were increased. Furthermore, MLN cells from FAHF-2-treated mice produced markedly less IL-4 and IL-5, but more IFN-gamma, and contained increased numbers of IFN-gamma-producing CD8(+) cells as compared with sham-treated mice. Conclusion FAHF-2 treatment established PN tolerance in this model, which persisted for at least 4-week post-treatment. This result was associated with modulation of intestinal T helper type 1 cell (Th 1) and Th2 cytokine production, and with increased numbers of mesenteric IFN-gamma-producing CD8(+) cells.