Objective To investigate the role of cyclophilin A (CypA) and CD147 in the process of skin aging. Methods Twenty cases of tissue samples from junior group(＜15 years old), middle age group(30-40 years old)or old age group (＞65 years old) were collected from photophobic and exposal parts of skin, respectively. Immunohistochemistry (IHC) and in situ hybridization (ISH) were carried out to semi-quantitatively detect the expression level of CyPA and CD147. Results IHC demonstrated that both CyPA and CD147 were expressed in both photophobic and exposal parts of normal human skin in all 3 groups. The expression levels of both CyPA and CD147 were increased with increase in age. There were significant differences in both CyPA and CD147 expression among 3 groups (P<0.05). CyPA and CD147 were also positively correlated in all 3 groups. Similar results were achieved by ISH. Conclusion The interaction between CD147 and CyPA might play an important role in the process of skin aging.