In the present study, combined treatment with etanercept and anakinra were tested in the streptozotocin-induced diabetic rats. Forty male Wistar albino rats were divided into 5 groups: healthy control (HC), diabetic control (DC), diabetic + anakinra (DAT), diabetic + etanercept (DET), and diabetic + etanercept + anakinra (DEAT). HC and DC groups received subcutaneous (s.c.) injection with a saline solution, while DAT and DET groups received anakinra (10 mg/kg per day, s.c.) or etanercept (10 mg/kg, twice a week, s.c.), and DEAT rats received both anakinra and etanercept treatments for 21 days after diabetes has developed. Anakinra and etanercept treatments significantly increased insulin and homeostatic model assessment α-cell function levels and decreased glucose levels compared to the DC group as single (DAT and DET) and combined treatments (DEAT). The thiobarbituric acid reactive substances level was significantly decreased in DAT group. The combine use of etanercept and anakinra can improve insulin and blood glucose in type 2 diabetic rats. The combined treatment of anakinra and etanercept together was more effective than single treatment and might have a potential new treatment strategy and to reduce the mortality and morbidity resulting from diabetes.