Background Insulin resistance is an underlying feature of both type 2 diabetes and metabolic syndrome.Currently,it is unclear whether nuclear factor (NF)-κB inducing kinase (NIK) plays a role in the development of insulin resistance.The present in vivo study investigated the roles of NIK and IKB kinase α (IKKα) in obesity-induced insulin resistance using animal models.Methods NIK expression was evaluated by Westem blotting in male Lepob mice and C57BL/6J mice fed a high-fat diet (HFD) (45％ fat).After metformin and sulfasalazine treatment,NIK expression was investigated during the improvement of insulin resistance.Results NIK was increased by about 1-fold in the renal tissues of Lepob mice and C57BL/6J mice fed a HFD for 12 weeks.After 1 and 3 weeks of high-fat feeding,we observed an almost 50％ decrease in NIK and IKKα expression in the liver and renal tissues of C57BL/6J mice.NIK expression was significantly lower in the liver and renal tissues of HFD-fed mice that were treated with insulin sensitizers,metformin and sulfasalazine.However,IKKα expression was increased after metformin treatment in both tissues.Conclusion These results suggest a possible role of NIK in the liver and renal tissues of insulin-resistant mice.