Background: Exercise deprivation has been concluded to have some negative effects on psychological well-being. This study was conducted to find out whether exercise deprivation may lead to morphine dependence in rats. Methods: Forty male Wistar rats weighing 162 ± 9 g were housed in clear plastic cages in groups of two under standard laboratory conditions. The study had two phases. In phase I, the animals were randomly divided into exercised (E) and unexercised (UE) groups (n = 20 each) and treadmill running was performed based on a standard protocol for three weeks. At the end of the training period, plasma β-endorphin levels were determined in four rats from each group. In phase II, the animals were provided with two bottles, one containing tap water and the other 25 mg/l morphine sulfate in tap water for a total of 12 weeks. At the end of this phase naloxone was injected intraperitoneally to precipitate morphine withdrawal Findings: There was no significant difference between UE and E groups in morphine consumption (mg/kg/wk) [group: F(1,14) = 0.2, P = 0.690; time: F(11,154) =18.72, P < 0.001; interaction: F(11,154) = 1.27 , P = 0.245]. No statistically significant difference between the two groups of animals was seen regarding withdrawal signs. Conclusion: The study showed that discontinuation of exercise does not increase the tendency of morphine dependence in rats. Keywords: Exercise dependence, Substance dependence, Oral morphine self-administration, Rat.