In this study, protective effect and immune response elicited by protein fractions LiRic1 (>75 kDa) and LiRic2 (<37 kDa) released by Leishmania infantum promastigotes were analysed in challenged BALB/c mice. Viable parasites were quantified in spleen and isolated CD4(+) and CD8(+) T cells were stimulated for evaluation of proliferative response and cytokine production. Immunization triggered 50.4-66.9% of parasite reduction. Stimulated CD4(+) T cells from challenged animals revealed high proliferation. IL-12 and IFN-gamma were released by CD4(+) T cells whereas IL-4 and IL-10 were impaired. LiRic1 and LiRic2 immunization gave partial protection and a CD4(+) Th1 response. LiRic2 generated IL-12 by CD8(+) T cells pointing to its participation in protective response. These results encourage further research on the development of a vaccine that provides long-lasting protection against zoonotic visceral leishmaniasis.