We previously found that Lactobacillus plantarum strain 06CC2 showed probiotic potential, and its oral administration effectively induced Th1 cytokine production and activated the Th1 immune response associated with intestinal immunity in mice. In this study, to evaluate its potential as a versatile oral adjuvant for treatment of viral infection, we assessed the immunomodulatory activity of 06CC2 on murine cutaneous herpes simplex virus type 1 (HSV-1) infection, in which a major immune defense system is a delayed-type hypersensitivity (DTH) reaction based on activation of the Th1 immune response, in relation to its oral efficacy for alleviation of herpetic symptoms. In the HSV-1 infection model, oral administration of 06CC2 (20 mg/mouse) twice daily for seven days starting two days before infection was significantly effective in delaying the development of skin lesions in the early phase of infection and reducing virus yields in the brain on day 4 after infection. In addition, 06CC2 significantly augmented the DTH reaction to inactivated HSV-1 antigen and elevated interferon (IFN)-γ production by HSV-1 antigen from splenocytes. On day 2, natural killer (NK) cell activity was significantly elevated, and the elevation was still observed on day 4. Furthermore, gene expressions of interleukin-12 receptor β2 and IFN-γ in Peyer's patches were augmented on day 4 by 06CC2 administration. Thus, 06CC2 was suggested to alleviate herpetic symptoms in mice in correlation with augmentation of the Th1 immune responses associated with NK cell activity through intestinal immunity. Strain 06CC2 may be a versatile oral adjuvant to activate Th1 immune response.