In the present study, treatment with MCC950 (10 mg/kg) was efficacious in ameliorating anxiety-like behaviors in L/D box, depression-like behaviors in TST and FST, cognitive disorders in MWM test, as well as decreasing hippocampal NLRP3, ASC, and IL-1β expression levels and caspase-1 activity in db/db mice. This evidence concerns the gene CASP1 and major depressive disorder.