Abstract: To investigate the relationship between phosphodiesterase（PDEs） expression and Staphylococcus aureus mastitis, the expression of all subtypes of PDE family except PDE6, PDE10 and PDE11 in cow mammary epithelial cells（bMECs）, mouse mammary epithelial cells（mMECs） and mouse mammary gland（mMG） was detected by PCR. Real-time fluorescence quantitative PCR was used to detect the expression difference of these PDE subtypes under the stimulation of Staphylococcus aureus and the effect of PDE4 inhibitor RO-20-1724 on the expression of inflammatory factors induced by Staphylococcus aureus. The results showed that PDE3B, 5A, 8B and 9A were highly expressed in bMECs, and PDE2A was highly expressed in mMECs, and PDE2A and 3A were highly expressed in mMG. The relative expression levels of PDE1C, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A and PDE8A genes in bMECs were significantly increased after 8 h of Staphylococcus aureus stimulation（P＜0.05 or P＜0.01）. The relative expression levels of PDE1B gene, 7A gene and 7B gene were significantly decreased（P＜0.05 or P＜0.01）. The relative expression levels of PDE1B, PDE1C, PDE2A, PDE3A, PDE4A, PDE4C, PDE4D and PDE5A in mMECs were significantly increased（P＜0.01）, while the relative expression levels of PDE7A were significantly decreased（P＜0.01）. The relative expression levels of PDE1B, PDE3A, PDE4C, PDE4D, PDE5A, PDE8A and PDE8B in mMG were significantly increased（P＜0.05 or P＜0.01）, while the relative expression levels of PDE1C, PDE4B and PDE7B were significantly decreased（P＜0.01）. Incubation with RO-20-1724 for 8 h significantly decreased the relative expression of mMECs IL-1β gene induced by Staphylococcus aureus. These results indicated that there were species differences in the expression of some subtypes of PDE family in mammary epithelial cells, and Staphylococcus aureus infection could cause changes in the expression of different PDE subtypes.