Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. Although viruses have been suggested to be a contributing environmental factor, conventional experimental MS mouse models do not account for this aspect. Here, we describe a mouse model to induce and evaluate demyelinating disease with both a viral and an immune component via ocular infection with a recombinant herpes simplex virus expressing murine interleukin-2. For complete details on the use and execution of this protocol, please refer to Hirose et al. (2020).