Severe acute respiratory syndrome (SARS) is a deadly and highly infectious disease caused by SARS Coronavirus (SARS-CoV). Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV; however, current knowledge of inactivated SARS-CoV vaccine is quite limited. We attempted to investigate the effects of different immunization protocols and adjuvant on the antibody responses to inactivated SARS-CoV vaccine. With an intraperitoneal (IP) immunization protocol, inactivated SARS-CoV alone induced significant amounts of SARS-CoV-specific IgG antibodies in sera and a small quantity of SARS-CoV-specific IgA antibodies in the genital tract and feces, but failed to induce any detectable SARS-CoV-specific IgA antibodies in sera, saliva, lung, and intestine, and the addition of CpG ODN 2006 had only a marginal effect on antibody production. In contrast, with an intranasal (IN) immunization protocol, inactivated SARS-CoV alone failed to induce any detectable SARS-CoV-specific IgA antibodies in sera, saliva, lung, and intestine, except for a small quantity of IgA antibodies in fecal extracts and the genital tract, along with IgG antibodies in sera, but when given with adjuvant CpG ODN 2006, inactivated SARS-CoV induced significant amounts of SARS-CoV-specific IgG antibodies in sera, and a detectable amount of SARS-CoV-specific IgA antibodies in sera and all tested mucosal secretions and tissues (i.e., saliva, the genital tract, fecal extract, lung, and intestine). On a neutralization assay, neutralizing activity with the IP immunization protocol was detected in sera and mucosal secretions (from the saliva and genital tract), but sera from the IN protocol failed to show any neutralizing activity. Our study demonstrated that inactivated SARS-CoV vaccine is promising, and our data provide a sound foundation for the development of an effective inactivated SARS-CoV vaccine.