Methylcobalamin (MeCbl) is an analog of vitamin B12 used to relieve peripheral neuropathy. In this study, we examined whether MeCbl inhibited mechanical allodynia (acute herpetic pain -AHP- and postherpetic neuralgia -PHN-) in mice infected with herpes simplex virus-1 (HSV-1). Mice were inoculated transdermally with HSV-1. Herpes zoster-like skin lesion peaked on day 7 after the inoculation, and was completely healed by day 20. Mechanical allodynia peaked on day 7-10 (AHP) post-inoculation, and was continuously observed after rash healing (PHN). Single administration of MeCbl inhibited mechanical allodynia in AHP phase. The anti-allodynic action of MeCbl was suppressed by naloxone, an opioid receptor antagonist, but not naloxone methiodide which has limited access to the CNS. Furthermore, repetitive administration of MeCbl from day 5 post-inoculation suppressed both AHP and PHN, and also promoted recovery of the peripheral nerve fibers decreased by HSV-1 infection in the footpad skin. These results suggest that activation of endogenous opioid system in the CNS and promotion of recovery of decreased peripheral nerve fibers are involved in the anti-allodynic actions of MeCbl in HSV-1-infected mice.