Microneme proteins (MICs) are important for Apicomplexan parasite invasion due to their adhesion to host cells. Several studies have indicated that MIC3 and MIC8 are important adhesion factors and potential vaccine candidates against neosporosis. In this study, we evaluated the protective efficacy of recombinant proteins and DNA vaccines of NcMIC3 and NcMIC8. BALB/c mice were immunized with rNcMIC3, rNcMIC8, pcDNA3.1-NcMIC3 and pcDNA3.1-NcMIC8 respectively, and challenged with tachyzoites. The immune responses were evaluated through cytokine, antibody measurements and the parasite burden in the mice brain tissues. Serological analysis showed that recombinant protein vaccines induced higher levels of immunoglobulin G (IgG) than other groups. The percentage of IgG1 and IgG2a in the recombinant protein groups was higher than the other groups, and with a predominance of IgG1 over IgG2a, suggesting that recombinant protein vaccines elicited a Th2-type immune response, while DNA vaccines mainly produce a Th1-type immune response. In addition, mice immunized with rNcMIC3 and rNcMIC8 a had lower parasite burden in brain tissue compared with the other groups. These results demonstrate that rNcMIC3 and rNcMIC8 could induce humoral and Th2-type immune response, leading to a considerable level of resistance against neosporosis.