The aim of this study was to evaluate the effect of minocycline on morphine withdrawal syndrome in male rats. Male Wistar rats (225–275g) were randomly divided in to six groups (n=8). Morphine was administered subcutaneously (sc) for nine days; day 1: 5mg/kg/12h, days 2,3: 10 mg/kg/12h, days 4,5: 15 mg/kh/12h, days 6,7: 20 mg/kg/12h, and days 8,9: 25 mg/kg/12h. Minocycline was injected just before the morphine injection twice daily. On day ninth, only the morning doses of morphine and minocycline were injected. Then, an hour after the last dose of morphine, naloxone (4 mg/kg’ ip) was injected and the withdrawal signs (jumping, rearing, genital grooming, abdomen writhing and wet dog shake) were recorded for 60 minutes. Animals received saline (1 ml/kg/12h, ip), or saline (1ml/kg/12h, ip) + morphine (10 mg/kg/12h, sc), or minocycline (10, 20, 40 mg/kg/12h, ip) + morphine (10 mg/kg/12h, sc). Results showed that minocycline decreased withdrawal syndrome significantly (p<0.001). Minocycline decreased morphine withdrawal syndrome, the possible mechanism being related to inhibition of nitric oxide/NMDA pathway.