In this study, we determined that hyperglycemia promoted acute liver injury and inflammatory immune responses by promoting liver‐resident macrophage NLRP3 inflammasome activation via the inhibition of the 5′ AMP‐activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) autophagy signaling pathways in a streptozotocin (STZ)‐induced hyperglycemic mouse model. This evidence concerns the gene NLRP3 and Hyperglycemia.