Abstract: To investigate the effects of nicotine on the expression of inflammation-related cytokines in the hippocampus of rats, a conditional place preference (CPP) device was used to establish the acquisition, extinction and reinstatement of nicotine CPP in rats at the nicotine doses of 0.2 and 0.6 mg/kg. A total of 23 inflammation-related cytokines were detected simultaneously in the hippocampus at different stages (acquisition, extinction and reinstatement) by the suspension chip technique. The one-way variance analysis was adopted to analyze the differential cytokine expressions in the hippocampus at different stages using a nicotine preference model. The results showed that:1) Nicotine promoted the expressions of interleukin (IL)-1α and IL-10 and inhibited the expressions of IL-6, IL-18, growth-related oncogene/keratinocyte chemoattractant (GRO/KC) and regulated upon activation normal T cell expressed and secreted factor (RANTES) at low and higher doses. 2) The GRO/KC level in rat hippocampus was susceptible to nicotine, which reduced GRO/KC expression, while the reduction effect was weakened during the acquisition-extinction stage and was restored to the level at the acquisition stage during the extinction-reinstatement stage, the evidence therefore suggested that GRO/KC might be involved in the potential anti-inflammatory mechanism of nicotine. 3) The variation trends of the other five cytokine levels were different or even contrary to GRO/KC. Further studies are needed to understand the inflammatory mechanism of nicotine through the rat and other animal inflammation models.