〔Abstract〕 Objective To investigate the effects of different doses of clozapine on the expression of amylase and pro-inflammatory cytokines [interleukin 1β(IL-1β),interleukin 6(IL-6),and tumor necrosis factor α(TNF-α)] in the serum and pancreatic tissue of male C57 BL/6 mice. Methods Male C57 BL/6 mice were randomly divided into four groups. Mice were treated with clozapine 5,10 and 20 mg/kg or an equal volume of saline by gavage. Mice blood was collected to examine the levels of amylase and pro-inflammatory cytokines( IL-1β,IL-6 and TNF-α) after14 days ofconsecutive gavage. Then the pancreases of the mice were dissected. Western blot was used to detect the expression of amylase,IL-1β,IL-6 and TNF-α protein in pancreatic tissue. Fluorescence quantitative PCR method was used to detect the expression of amylase,IL-1β,IL-6 and TNF-α mRNA in pancreatic tissue. Results Compared with the control group,serum amylase levels significantly increased in the 10 and 20 mg/kg clozapine groups( P<0. 01 and P<0. 001). Compared with the control group,serum IL-1β level of the three clozapine groups increased in a dose-dependent manner( P<0. 01,P<0. 001). Compared with the control group,serum IL-6 level decreased in the clozapine 5 mg/kg group( P<0. 05). Clozapine dose-dependently increased the expression of amylase,IL-1β,IL-6 and TNF-α protein and mRNA in pancreatic tissues of mice,and the differences were statistically significant compared with the normal saline group( P<0. 01). Conclusion Clozapine reliably increased the levels of serum amylase and IL-1β． Clozapine also increased the expression of amylase and pro-inflammatory cytokines IL-1β,IL-6 and TNF-α in pancreatic tissue,which may be one of the pathogenesis of clozapine-induced hyperamylasemia and even pancreatitis.