Objective To evaluate toxicopathological changes of central nervous system in rats at different morphine-dependent time. Methods Animal model of morphine-dependence in rats was established by subcutaneous injection of morphine. Histopathologic changes of coeruleus, periaqueductal gray, substantia nigra, lenticula, corpus amygdaloideun and hippocampus in morphine-dependent rats were observed by microscopy and electron microscopy, and synaptic numbers were counted and compared with those in control animals. Results Six morphine dependence-related regions in morphine-dependent groups were observed. Pyknosis or swelling of the nerve cells, swollen nerve fibers, swollen and deformed mitochondria were detected. Dilated endoplasmic reticulum and disaggregated polyribosomes were observed with increased number in synapsis. Gliocytosis and subpial infiltration of lymphocytes and monocytes became more obvious with extension of dependent time, and glial nodules were formed. Synaptic numbers were significantly increased in morphine-dependent groups at 4 or 8 weeks as compared with those in control group(P