Morphine reexposure induces the decrease of receptor for activated C-kinase 1 protein (RACK1) levels in frontal cortex, and the increase of p-ERK (extracellular signal-regulated kinase) levels in mouse frontal cortex, striatum, hippocampus and nucleus accumbens (NAcc). Moreover, RACK1 is associated with the core kinases of the ERK pathway, Raf, MEK, and ERK. The purpose of this study is to investigate the effect of overexpression of RACK1 on the conditioned place preference (CPP) and the level of p-ERK in morphine reexposure mice. Mice were subcutaneously injected with morphine on the 2nd, 4th, 6th, and the 8th day, saline was delivered the next day. After mice showed place preference, RACK1 was administered by intraventricular injection 20 minutes after injection of morphine on the 11th, 13th, 15th, and 17th day. CPP was measured on the 18th day. It was found that morphine reexposured mice showed a decreased RACK1 level in the frontal cortex, striatum and an increased RACK1 level in hippocampus and NAcc, but this effect was reversed after administration of RACK1. In this study we demonstrated that RACK1 decreased p-ERK and erased CPP during reexposure of morphine and there was no an effect in reexposure saline mice. It strongly suggests that RACK1 may play a crucial role in morphine reexposured mice and the RACK1 has the potential to be a remedy to the morphine reward.