The present study was designed to investigate the protective effect of Sophoraflavanone G (SG) on streptozotocin (STZ)-induced diabetic rats. The rats were intraperitoneally injected with STZ (35mg/kg). 7days later, the rats were intragastrically administered with Metformin (MET, 150mg/kg), SG (20mg/kg) or SG (40mg/kg) once daily for consecutive 30 days. The animals were anaesthetized, the blood and liver samples were also collected for further assay. SG significantly decreased the serum levels of glucose, insulin, aspartate transaminase (AST), alanine aminotransferase (ALT). In addition, SG increased superoxide dismutase (SOD) activity and inhibited malondialdehyde (MDA) content in serum. SG also ameliorated the histopathological condition. Furthermore, SG attenuated the expressions of thioredoxin (Trx), thioredoxin-interacting protein (Txnip) and the phosphorylations of inhibitory kappa B kinase (IKK)α, IKKβ, nuclear factor-κB inhibitory proteins (IκB)α, nuclear factor κB (NF-κB). These findings demonstrated that SG showed beneficial effects on STZ-induced diabetic rats.