Objective To explore the role of microRNA⁃223（miR⁃223）in ketamine⁃induced pyrolysis of hippocampal neurons in rats at a developmental phase by regulating the Nod⁃like receptor pyrin domain⁃containing protein 3（NLRP3）/cysteinyl aspartate specific proteinase 1（Caspase⁃1）pathway. Methods Rats were divided into a control group，ketamine group，agomir⁃NC group，agomir⁃223 group，agomir⁃223+BAY11⁃7082 group，10 for each group. Western blot was used to detect expressions of NLRP3，cleaved Caspase⁃1 and GSDMD⁃N in the rat hippocampus. Results As compared with the control group，the incubation period，hippocampal histopathology， neuronal apoptosis，levels of interleukin⁃18（IL⁃18），interleukin⁃1β（IL⁃1β），NLRP3，cleaved Caspase⁃1，and GSDMD⁃N increased in the ketamine group；while the number of crossing platforms，the proportion of time staying in the third quadrant，and the level of miR⁃223 reduced（P < 0.05）. As compared with the ketamine group，the incubation period，hippocampal histopathology，neuronal apoptosis，levels of IL ⁃18，IL ⁃1β，NLRP3，cleaved Caspase⁃1，and GSDMD⁃N reduced in the agomir⁃223 group，whereas the number of crossing platforms，the proportion of time staying in the third quadrant，and the level of miR ⁃ 223 increased（P < 0.05）. Conclusions Overexpression of miR⁃223 may improve ketamine⁃induced hippocampal neuronal pyrolysis in rats at a developmental phase by inhibiting the NLRP3/Caspase⁃1 pathway.