Granulocyte–monocyte colony-stimulating factor (GM-CSF) regulates the function of antigen-presenting cells (APCs) and has been broadly used as the adjuvant. Here, we tested whether intranasal delivery of GM-CSF can improve the contraception of mouse zona pellucida 3 (mZP3) DNA vaccine. Our results showed that co-administration of GM-CSF and mZP3 DNA vaccine increased the levels of secretory IgA (sIgA) and IgG antibodies in vaginal washes and serum, respectively. Co-administration enhanced Th2 responses through improving the maturation of dendritic cells. Importantly, GM-CSF significantly reduced the fertility rate and mean litter size induced by mZP3 DNA vaccine alone without interfering the normal follicular development. These data suggest that GM-CSF could be used as adjuvant to develop immunocontraceptive vaccine.