Objective: The aim of this study was to evaluate the effect of minocycline on morphine withdrawal syndrome in male rat. Methods: male wistar rats (225 – 275 g) were selected (n=8) randomly and divided in to six groups: In order to evaluate the effect of minocycline on morphine withdrawal syndrome. Morphine was administered subcutaneously for nine days: Day 1: 5mg/kg/12h, Day 2,3: 10 mg/kg/12h, Day 4,5: 15 mg/kh/12h, Day 6,7: 20 mg/kg/12h, Day 8,9: 25 mg/kg/12h. On ninth day only the morning dose of morphine and minocycline were injected. Minocycline was injected just before the morphine injection twice a day, on ninth day an hour after the last dose of morphine, naloxone ( 4 mg/kg’ ip) 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) }. Result: Results showed that minocycline decreased withdrawal syndrome significantly (p<0.001). Conclusion: minocycline decreased the withdrawal syndrome of morphine and the possible mechanism is related to inhibition of Nitric oxide / N – methyl D – aspartat pathway.