Background: Large numbers of - CD8+ T cells were observed in atopic dermatitis (AD) skin, and monocytes from AD patients showed increased prostaglandin E2 production. However, little is known about the expression of substance P (SP) and its receptor NK1R in blood leukocytes of patients with AD. Objective: To explore the expression of SP and NK1R in leukocytes of AD and the influence of allergens on SP and NK1R expression. Methods: The expression levels of SP and NK1R in patients with AD were examined by flow cytometry, ELISA and a mouse AD model. Results: The plasma SP level was 4.9- fold higher in patients with AD than in HC subjects. Both the percentage of SP expression in the population and mean fluorescence intensity (MFI) of SP expression were elevated in - CD8+ T cells in the blood of AD patients. However, both the - CD14+ NK1R+ population and MFI of NK1R expression on - CD14+ cells were enhanced in the blood of AD patients. Allergens ASWE, HDME and PPE failed to up-regulate SP expression in - CD8+ T cells. However, allergens ASWE and HDME both enhanced NK1R expression on - CD14+ blood leukocytes regardless of AD or HC subjects. OVA- sensitized AD mice showed an elevated proportion and MFI of SP-expressing - CD8+ T cells in the blood, which agrees with the SP expression situation in human AD blood. Injection of SP into mouse skin did not up- regulate NK1R expression on monocytes. Conclusions: An elevated plasma SP level, up- regulated expression of SP and NK1R indicate that the SP/NK1R complex is important in the development of AD. Therefore, SP and NK1R antagonist or blocker agents may help to treat patients with AD.