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Objective To study the effects of methamphetamine on the expression of 5- Hydroxytryptophan (5-HT)， interleukin-6 (IL-6) and nuclear fact kappa B (NF-κB) in rats' hippocampus. Methods Thirty SD rats were randomly allocated into normal control group，METH1d group，METH3d group， METH5d group and METH7d group，with 6 rats in each group．Intraperitoneal injections of METH [15mg/(kg·time)] were conducted at 9:00am and 21:00pm every day．After injection，scoring was performed in combination with observation on their stereotyped behavior. We established different models for rats suffering from 1-day，3-day，5-day，and 7-day METH acute poisoning. After 24 hours of the last intraperitoneal injections of METH，hippocampal tissues were isolated．Enzyme linked immunoorbent assay (ELISA) was applied to detect the expression level of 5-HT and IL-6 in rats hippocampus. Western blot was used to detect the expression level of NF-κBp65．Results Compared with the control group，the expression of 5-HT was reduced in different METH groups，and the decrease was statistically significant in METH5d and METH7d groups (with P<0.05 and P<0.01 respectively) . Compared with the control group，the expression of IL-6 was increased in different METH groups， and the increase was statistically significant in METH5d and METH7d groups (with P<0.05 and P<0.01 respectively) . Compared with the control group， the expression of NF-κB was increased in different groups， and the increase was statistically significant only in METH7d group (P<0.01) . Conclusion METH administration could result in a significant reduce of 5-HT expression and increases of IL-6 and NF-κB expressions in rats hippocampus. [ABSTRACT FROM AUTHOR]