In this report, we proposed and verified our hypothesis that chemerin is enriched by CCRL2 in chemerin-induced diabetic dams’ offspring brain tissue, and chemerin aggregation in the offspring brain induced a decrease in neurons, accumulation of macrophages, and activation of pyroptosis in macrophages in a ChemR23-dependent manner, thereby leading to nerve damage and cognitive deficits in the offspring. Here, CMKLR1 is linked to Cognitive impairment.