Ricin is a potent plant toxin known to cause cell death by inhibiting protein synthesis. The currently used vaccine is prepared mainly from biohazardous toxin. Thus, this research studied an alternative protein, Ricinus communis agglutinin (RCA), which has the same structure as ricin but much lower toxicity, and demonstrated that RCA provided sufficient protection against ricin in a murine model. Method: The serum antibody levels were determined using ELISA. The ricin-neutralized antibody, protection against ricin and cross-protection against abrin were assayed under direct challenge of lethal-dose ricin. Results: After four cycles of immunization, mice evoked high levels of serum antibodies and survived lethal doses of ricin. Immunized mice also elicited partial cross-protection against the challenges of abrin. The serum antibody titer of RCA-immunized mice was almost the same as that of ricin toxoid-immunized mice. Serum antibody titers induced by i.p. route immunization with either RCA or ricin toxoid were slightly higher than those induced by oral route with RCA, but there is no difference between RCA (i.p.) and ricin toxoid (i.p.) or RCA (i.p.) and RCA (oral). Conclusions: Serum from the immunized animals that had received RCA either i.p. or orally showed completely neutralized ricin activity. This is the first study demonstrating the potential use of RCA as an oral vaccine candidate for ricin protection.