Objective To investigate the roles of cyclooxygenase-2 (COX-2) and its signal transduction pathway related molecules in the pathogenesis of autoimmune-type recurrent spontaneous abortion (RSA). Methods Eighty-three BALB/c mice were divided into experiment group, uterine cavity injection control group and normal pregnancy control group. Experiment group was subdivided into uterine cavity human β2 glycoprotein-1 (β2GP1) injection group (n=15), abdominal cavity β2GP1 injection group (n=10) and subcutaneous β2GP1 injection group (n=14). Uterine cavity injection control group was subdivided into uterine cavity normal saline (NS) injection group (n=10), uterine cavity unrelated protein injection group (n=6) and uterine cavity adjuvant injection group (n=13). Mice in normal pregnancy control group (n=15) did not receive any intervention. The embryo loss rates, the abortion rates and the average weight of placenta were compared among groups. The expression of COX-2 in placenta and its signal transduction pathway related molecules prostaglandin D2 （PGD2）, interferon-inducible protein (IP), peroxisome proliferators activator receptors alpha (PPARα) and PPARγ mRNA was detected by RT-PCR. Results The embryo loss rates in subgroups of experiment group were significantly higher than that in normal pregnancy control group (P<0.001), and the average weight of placenta in subgroups of experiment group was significantly lower than that in normal pregnancy control group (P<0.05). The abortion rate in uterine cavity β2GP1 injection group was significantly higher than those in the other groups （P<0.05）. The expression of COX-2, PGD2, IP, PPARα and PPARγ mRNA in placenta in subgroups of experiment group was significantly lower than that in normal pregnancy control group (P<0.05), and the expression of COX-2, PGD2, IP, PPARα and PPARγ mRNA in placenta in uterine cavity β2GP1 injection group was significantly lower than that in uterine cavity injection control group （P<0.05）. Conclusion Uterine cavity injection of human β2GP-1 can successfully establish mouse model which is consistent with the features of autoimmune-type RSA, and COX-2 and its signal transduction pathway related molecules may play important roles in the pathogenesis of autoimmune-type RSA.