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Depression is a chronic and progressive syndrome and commonly associated with several neuropsychiatric comorbidities, of which depression is the most studied. It has been demonstrated that statins also have anti-inflammatory and immunomodulatory properties, which being explored for potential benefits in depression. However, the role of statins in the treatment of diabetes-related depression has not been well examined. Herein, we investigated the effects of atorvastatin on depressive behaviors and neuroinflammation in streptozotocin-induced diabetic mice. Our data indicated that oral administration of atorvastatin at 10 or 20 mg/kg for 3 weeks markedly ameliorated diabetes-associated depressive behaviors reflected by better performance in sucrose preference test (SPT), tail suspension test (TST), and novelty-suppressed feeding test (NSFT). The study further showed that atrovastatin decreased the expression of nucleus NF-κB p65 expression and ameliorated neuroinflammatory responses in prefrontal cortex as evidenced by less Iba-1-positive cells and lower inflammatory mediators including IL-1β and TNF-α. As expected, atorvastatin-treated diabetic mice exhibited significant improvement of hyperlipidemia rather than hyperglycemia. These results suggest that atorvastatin has the potential to be employed as a therapy for diabetes-related depression.