Objective：To investigate the roles of periostin and thymic stromal lymphopoietin（TSLP） in chronic pruritus by analyzing the pathological changes of the skin lesions. Methods：Samples of skin lesions from 42 patients with skin pruritus over 6 weeks and samples of normal skin from 23 general persons were collected from December 2014 to December 2016. The histopathological changes of the samples were detected by the hematoxylin-eosin（HE） staining，and the expressions of periostin and TSLP in skin tissues by the immunohistochemistry（IHC）. Then the thickness of epidermis and the expressions of periostin and TSLP were compared between the two groups. Results：HE staining showed that the epidermis in patients thickened significantly compared with that in the control [（477.70±14.89） μm vs. （94.28±6.58） μm，t=40.800，P=0.000]. In skin lesion samples，parakeratosis and hyperkeratosis were observed in the stratum corneum，and the infiltration of the inflammatory cells was observed in the dermis. IHC staining showed that the expressions of periostin and TSLP in chronic pruritus group were significantly higher than those in the control group respectively[（7.33±3.20） vs. （0.65±0.65），t=13.060，P=0.000] and [（8.48±2.60） vs. （0.61±0.66），t=18.580，P=0.000]. Specifically，periostin was mainly expressed in the dermis，outside of the hair follicles and sebaceous glands，while TSLP was mainly expressed in the epidermis，inside of the hair follicles and sebaceous glands. Conclusion：Periostin/TSLP-mediated T help cell 2（Th2） type immune response is involved in the pathogenesis and development of chronic pruritus.