Objective  To detect the expression of CD131 in rat renal tubular epithelial cells and explore its possible role in the process that erythropoietin (EPO) inhibits renal tubular cells apoptosis induced by high glucose.Methods  The rat renal tubular epithelial cells NRK-52E were subcultured and randomly divided into normal control group, high glucose group, high glucose+EPO group, high glucose+EPO+scramble siRNA group, high glucose+EPO+EPO receptor (EPOR)  siRNA group and high glucose+EPO+CD131 siRNA group. The expressions of EPOR and CD131 in NRK-52E cell were detected by realtime fluorescence quantitative PCR (RT-qPCR), Western blot and immunofluorescence, and the binding between EPOR and CD131 in NRK-52E cell was detected by co-immunoprecipitation (co-IP). The apoptosis of NRK-52E cell was detected by TUNEL, and the expression of Caspase-3 in NRK-52E cells was detected by RT-qPCR and Western blot.Results  EPOR and CD131 were expressed in NRK-52E cells by RT-qPCR and Western blot, and the expression of EPOR and CD131 in NRK-52E cells increased after high glucose incubation.Immunofluorescence assay showed that EPOR and CD131 were co-localized in NRK-52E cells, and co-IP assay showed that EPOR and CD131 were combined in NRK-52E cells. TUNEL assay showed that the apoptosis rate of NRK-52E cells was significantly increased in the high glucose group compared with the normal control group. Compared with the high glucose+EPO group, the apoptosis rate of NRK-52E cells was significantly increased in the EPOR siRNA and CD131 siRNA interference groups.Compared with the normal control group, the expression of Caspase-3 in NRK-52E cells was significantly increased in the high glucose group. After the inhibition of EPOR and CD131 by siRNA interference, the inhibition effect of EPO on caspase-3 expression was weakened.Conclusions  Rat renal tubular epithelial cells NRK-52E expressed EPOR and CD131, they could form EPOR-CD131 heterodimer in NRK-52E cells, that mediated the anti-apoptotic effect of EPO on NRK-52E cell induced by high glucose.