Objective: To investigate the protective effect of P-glycoprotein up-regulated by ulinastatin (UTI) on HK-2 cells during paraquat (PQ) -induced injury and its underlying mechanisms. Methods: The re- search was divided into two parts. The first part of the research was divided into normal control group, PQ group, UTI+PQ group, UTI control group. The second part of the research was divided into negative virus group (including control group, PQ group, PQU+TI group, UTI group) and P-gp siRNA group (including control group, PQ group, PQU+TI group, UTI group) . Negative virus group: the cells were transfected into the blank virus; siRNA P-gp group: the cells were transfected with P-gp siRNA virus. HK-2 cells were routinely cultured. After 800 μmol/L PQ treatment, the changes of P-gp protein levels in the HK-2 cells were determined by West-ern-blot (WB) . Then, transfected lentivirus bringing P-gp silent gene, the cell viability was determined by CCK-8 assay, the expression of P-gp in the cells after transfection was detected by WB and the concentration of PQ in HK-2 cells were measured by high performance liquid chromatography (HPLC) . Results: Compared with the normal control group, the P-gp expression of PQ group had no significantly changes (P>0.05) . Compared with the PQ group, the P-gp expression of UTI+PQ group significantly increased (P>0.05) . Compared with the corre-sponding control siRNA group, the P-gp siRNA group had no significantly changes in cell viability (P>0.05) . and significantly decreased in P-gp expression. Compared with the corresponding control siRNA group, the P-gp siRNA group had no significantly changes in PQ concentration in HK-2 cell (P>0.05) , but compared with P-gp siRNA PQ group, the PQ concentration of P-gp siRNA PQ+UTI group significantly decrease (P<0.05) . Conclusion: UTI significantly reduced the accumulation of PQ in HK-2 cells and increased the viability of HK-2 cells in vitro may be not by increased P-gp activity. UTI could significantly reduce HK-2 cell injury induced by PQ in vitro and improve the survival rate of HK-2 cells. It may not be related to the up regulation of P-gp expres-sion.