In recent years, the association between neuroinflammation and opioid dependence has attracted considerable attention. Curcumin, a component of the Curcuma longa, has been shown to act as a suppressor of glial cells and inflammatory cytokines. The main goal of this study was to explore the attenuating effects of curcumin on morphine dependence with a focus on neuroinflammation and μ-opioid receptors in the rat prefrontal cortex. To induce morphine dependence in male Wistar rats, morphine was administered i.p. once daily for 18 days in an escalating dose of 10, 20, and 40 mg/kg. Curcumin (2.5, 5, and 10 mg/kg, i.p.) was given from the days 10th to 18th. Immunofluorescence staining and ELISA methods were used to evaluate glial cells activity and inflammatory cytokines levels, respectively. Western blotting was used to evaluate the expression of μ-opioid receptors. The administration of curcumin (2.5, 5, and 10 mg/kg) for 9 days significantly attenuated the symptoms of morphine withdrawal syndrome. The prefrontal cortex concentration of TNF-α and IL-6 was also reduced by curcumin (2.5, 5, and 10 mg/kg) significantly. Furthermore, curcumin decreased the number of Iba1 and GFAP positive cells in morphine-dependent rats. Moreover, the expression of μ-opioid receptors was significantly reduced by curcumin (10 mg/kg). The results of this study demonstrate that curcumin attenuates morphine dependence in rats through an inhibitory effect on neuroinflammation and a decrease in the expression of μ-opioid receptors in the prefrontal cortex.