Lactoferrin (LF), a multifunctional milk protein, is known to inhibit in vitro infection by viruses such as herpes simplex virus type 1 (HSV-1). We evaluated the influence of LF feeding on the HSV-1 cutaneous infection of mice. Bovine LF was administered to mice and, after 10 d, the mice were infected with HSV-1. LF administration did not affect the viral clearance in the skin, but inhibited the appearance of skin lesions. LF prevented body weight loss and the decrease of splenocyte number associated with HSV-1 infection. LF increased the serum interleukin (IL)-18 level and splenocyte production of interferon-gamma and IL-12. These results suggest that LF feeding was not effective for eradication of the virus, but may contribute to the maintenance of homeostasis and the concomitant increases of cytokine responses during HSV-1 infection.