Introduction: Medical management for alcohol abuse has limitations. Alcohol consumption activates Nmethyl-(D)-aspartate receptors and release of nitric oxide which can be inhibited by minocycline as it readily crosses blood brain barrier and may have effect on alcohol consumption. Thus, study objective is to evaluate the effect of minocycline on rewarding property, extinction and the reinstatement phenomenon induced by alcohol in a model of conditioned place preference (CPP) in mice. Methodology: To evaluate rewarding effects of alcohol, CPP procedure consisted of 4 parts, including adaptation (day 1), pre-conditioning test (day 2), conditionings with alcohol (days 3, 5, 7 and 9) or saline (days 4, 6, 8 and 10) and postconditioning test (day 11) conducted on 11 consecutive days. The groups included were saline treated group (alcohol control), naltrexone -1 mg/kg (positive control), and minocycline in the doses of 10, 30 and 50 mg/kg. To evaluate the effect of minocycline on alcohol relapse, CPP procedure consisted 6 parts, the first 4 were the same as enumerated above followed by extinction (days 12-16) and reinstatement phase (day 17). Results: The time spent in alcohol paired compartment by different groups, revealed that minocycline and naltrexone significantly attenuated alcohol-induced place preference compared to alcohol control (p <0.05). Pretreatment with minocycline and naltrexone blocked reinstatement of extinguished CPP. Conclusion: Minocycline may have a role in attenuating the rewarding property of alcohol and prevent alcohol relapse. (C) 2017 Elsevier B.V. All rights reserved.