Stress has been demonstrated to play an important role in hair follicle function and the pathogenesis of some hair disorders. The central hypothalamic-pituitary-adrenal (HPA) axis is activated by stress stimuli, synthesizes and releases various components and eventually induces the pathogenesis and recurrence of peripheral diseases. Our aim is to compare the different responses under exposure of stress in hair follicle function among different mouse strains, and to detect the involvement of the central HPA axis after stress in hair follicle growth and melanogenesis. In this study, we exposed different mouse strains (C57BL/6, CBA/J, C3H/HeN, BALB/c and ICR) to a 21-day chronic restraint stress protocol and selected C57BL/6, CBA/J and BALB/c mice for further study because of their significant behavioral alterations. Then, we evaluated and compared the different responses and sensitivity to chronic restraint stress in hair follicle function and central HPA axis among the selected strains. The results showed that expression of POMC, CRF and GR mRNA and protein and serum levels of corticosterone were inhibited in response to stress. These findings suggested that chronic restraint stress may inhibit hair follicle growth and melanogenesis via regulating the key elements of the central HPA axis. In addition, the results revealed different mouse strains exhibit different responses in the central HPA axis and hair follicle after stress exposure. C57BL/6 might be the most sensitive strain among the three strains tested as well as an appropriate strain to study possible pathophysiological mechanisms by which the nervous system influences skin function and screen dermatological drugs suitable for psychotherapy. We believe the current study will provide some useful information for researchers who are interested in the bidirectional communication between the nervous and skin systems and the management of stress-induced cutaneous diseases.