Persistence of the corpus luteum (CL) in cattle usually occurs during the puerperium and is associated with interference of prostaglandin (PG) F(2α) release from the uterus. The objective of the present study was to determine for the first time the gene expressions in the persistent CL compared with the CL of pregnancy and cyclic CL. Three types of CL biopsy samples were collected from 32 lactating Holstein cows: (1) CL persisting for 29 to 33 days after the first ovulation postpartum (persistent CL, n=9), (2) CL between days 29 and 33 of early pregnancy (CL of pregnancy, n=8) and (3) CL between days 10 and 13 of the estrous cycle (cyclic CL, n=27). mRNA expression of 2',5'-oligoadenylate synthetase-1 was upregulated only in the CL of pregnancy, confirming exposure to interferon-τ (IFNT) produced by trophoblasts in pregnant cows. mRNA expressions of immune tolerance-related factors (PGES and forkhead/winged helix transcription factor 3) were upregulated in the CL of pregnancy but not in the persistent CL, suggesting that IFNT controls upregulation of these genes. mRNA expression relating to some of the major systems such as lymphangiogenesis, inflammation and apoptosis were similarly upregulated in the persistent CL and the CL of pregnancy but not in the cyclic CL. The results suggest that the persistent CL may survive for a long period without changes in local immune tolerance but develops several major systems required for CL maintenance similar to the CL of pregnancy.