Abstract: Acute drug use modifies brain function in critical ways, and prolonged drug use causes pervasive changes in brain function that persist long after withdrawal. Our previous studies proved that acute or four-day morphine injection impaired mice spatial recognition memory in the Y-maze, but the impairment was short and reversible. In the present study, morphine or saline (40 mg/ kg·day, ip) was injected into mice for 21 days. Spatial recognition memory was tested in the Y-maze on the 2nd, 9th and 19th withdrawal day. Our results showed that spatial recognition memory of morphine-injected mice was impaired on each of the three test days. Our study clearly suggests that long-term morphine use leads to more persistent impairments of spatial recognition memory.