Previously, we reported that expression of Rho/Rho-associated kinase (Rho/ROCK) pathway related genes in the rat brain were decreased after chronic administration of antidepressants, imipramine and sertraline. Then, we hypothesized that inhibition of ROCK would serve as a medication to treat stress-related mental disorders. In this study, we investigated the effect of a ROCK inhibitor, fasudil, using social defeat stress (SDS) mouse, which is considered as an animal model of stress-related mental disorders. As expected, SDS mice showed significant increase in the immobility compared with control mice in forced swim test. Interestingly, administration of fasudil during the stress exposure significantly decreased the immobility, while no significant effect was observed in SDS mice treated with fasudil after the stress exposure. Our results may suggest that fasudil would serve as a preventive medication for stress-related mental disorders. Since fasudil has already been used clinically for the treatment of cerebral vasospasm, clinical trials to examine the efficacy of fasudil in patients with stress-related mental disorders are warranted.