Objective To investigate the protective effect of apigenin on renal tubular epithelial cells(HK-2)induced by hyperglycemia and its potential mechanism.Methods HK-2 cells were incubated with d-glucose to establish an in vitro diabetic nephropathy model.Cell viability,apoptosis and oxidative stress were assessed.The mRNA levels of nuclear factor erythroid-2 related factor 2(Nrf2),heme oxygenase-1(HO-1)and epoxy chloropropane Kelch sample related protein-1(Keap1)were measured by quantitative real-time-PCR(q-PCR).Western blot analysis was performed to measure the protein expression of Nrf2.Results In HK-2 cells,high glucose decreased cell viability in a concentration-and time-dependent manner.Apigenin improved the viability of HK-2 cells under high glucose stress,reduced apoptosis and proinflammatory cytokine production,and inhibited the oxidative stress.Apigenin increased mRNA expression of Nrf2 and HO-1,increased expression of Nrf2 protein and reduced the mRNA level of Keap1.Inhibition of Nrf2 using small interfering RNA(siRNA)abolished the protective effects of apigenin on HK-2 cells under high glucose stress.Conclusion Apigenin treatment can alleviate the damage of HK-2 cells under high glucose stress,and exert the anti-oxidation and anti-inflammation effects through Keap1-Nrf2-ARE pathway.