Neuroinflammatory signaling pathways in the central nervous system are of current interest as potential pharmacotherapy targets for alcohol dependence. In this study, we examined the ability of ibudilast, a non‐selective phosphodiesterase inhibitor, to reduce alcohol drinking and relapse in alcohol‐preferring P rats, high‐alcohol drinking HAD1 rats, and in mice made dependent on alcohol through cycles of alcohol vapor exposure. When administered twice daily, ibudilast reduced alcohol drinking in rats by approximately 50% and reduced drinking by alcohol‐dependent mice at doses which had no effect in non‐dependent mice. These findings support the viability of ibudilast as a possible treatment for alcohol dependence.