Morphine induces adaptive changes in gene expression throughout the reward circuitry of brain. Recent research has proven the functional interactions between opioid and endogenous cannabinoid system in the central nervous system (CNS). The cannabinoid receptor 1 (CB1-R) is one of the receptors that mediate the actions of cannabinoids and endocannabinoids in the CNS. Here, we investigated the expression of CB1-R in mRNA and protein levels in the brains of rats treated with acute and repeated morphine. Three groups of rats received intraperitoneal injections (ip injections) of saline, acute morphine (10 mg/kg) and repeated morphine (10 mg/kg, twice daily for 12 consecutive days), and the mRNA levels and protein expressions of CB1-R were examined. RT-PCR and western blot analyses supported that both mRNA and protein levels of CB1-R in cortex, cerebellum and hippocampus were increased by repeated morphine treatment. However, the mRNA level in cerebellum was down-regulated only after acute morphine treatment and would returned to basal levels later. We used immunohistochemistry techniques to determine the functional expression of CB1-R in morphine treated rat’s brain. Enzyme-Linked Immunosorbent Assay (ELISA) revealed the significant increase of cytokine (IL-1beta, IL-6) levels in the repeated morphine treatment rats’ cortex and hippocampus regions, which are both addiction-related brain areas. In addition, the results from RT-PCR and western blot assay indicated that the expression of CB1-R was directly increased by morphine treatment in vitro. All the results indicated that the CB1-R expression could be changed by morphine exposure and it might be involved in neural immune function, which provided a potential target for neurogenic disease treatment.