We investigated the effects of the aqueous extract of Epimedii Herba (AEEH) on the induction of oral tolerance. Oral tolerance was induced in mice by giving an oral administration of 20 mg ovalbumin (OVA) 7 d before immunization with the antigen. AEEH at 40 mg/kg was given orally daily for 6 d from 24 h after the feeding of OVA. The results showed that oral administration of OVA greatly suppressed total serum and antigen-specific immunoglobulin (Ig) levels, phagocytic activity and delayed-type hypersensitivity (DTH) reaction to the antigen. The suppression of these immune responses to OVA by the oral antigen was associated with a marked reduction of the production of interferon-γ (IFN-γ) and interleukin-4 (IL-4) from spleen cells. However, AEEH treatment significantly blocked the suppression of total serum and antigen-specific IgG2a antibodies, phagocytic activity and DTH response by the oral OVA. The suppression of IFN-γ production by the oral antigen was also greatly decreased by AEEH treatment. Therefore, AEEH appears to be effective in preventing the induction of oral tolerance to OVA.