〔Abstract〕 Objective To investigate the effect of inhibition of p38 MAPK signaling pathway on renal cell apoptosis in rabbits with urosepsis and its mechanism. Methods Sixty New Zealand rabbits were randomly divided into 4 groups: sham operation group(sham),model group(model),p38 MAPK inhibitor SB203580 group(SB203580) and SB203580+p53 activator Nutlin-3 group(SB203580 + Nutlin-3),with 15 rabbits in each group.The urosepsis model was made by injecting Escherichia coli into the proximal end of the ureter.Intravenous injection of 30 μg/kg SB203580 or intraperitoneal injection of 128 mg/kg Nutlin-3 was used for intervention at 30 minutes before the operation, once daily, for a total of 3 d.The rectal temperature, respiratory rate and heart rate of the 4 groups of New Zealand rabbits were recorded at 24 h, 48 h and 72 h after operation.The automatic analyzer detected the white blood cell count, serum creatinine and urea nitrogen content.ELISA was used to detect the levels of serum Interleukin-1β(IL-1β),Interleukin-6(IL-6) and Tumor necrosis factor-α(TNF-α). Renal tissue was taken for TUNEL staining to observe the apoptosis; qRT-PCR method was used to detect the expression of MDM2 and p53 mRNA in renal tissue; Western blot method was used to detect the expression of Cleaved caspase-3,Bax, Bcl-2,p38 MAPK,p-p38 MAPK,MDM2,p53 and PUMA protein levels in renal tissue. Results Compared with the Model group, rabbits rectal temperature, respiratory rate, heart rate, white blood cell count, serum IL-1β,IL-6 and TNF-α levels, and serum creatinine and urea nitrogen levels reduced in the SB203580 group(P<0.05),and cell apoptosis rate of renal tissue, the mRNA expression of p53 and the proteins expression of p53,Cleaved caspase-3,Bax, PUMA and p-p38 MAPK decreased(P<0.05),while the expression levels of MDM2 mRNA and MDM2,Bcl-2 proteins increased(P<0.05).Compared with the SB203580 group, the rabbits rectal temperature, respiratory rate, heart rate, white blood cell count, serum IL-1β,IL-6 and TNF-α levels, and serum creatinine and urea nitrogen levels increased in the SB203580+Nutlin-3 group(P<0.05),and renal cell apoptosis rate, the mRNA expression of p53 and the proteins expression of p53,Cleaved caspase-3,Bax and PUMA increased(P<0.05),the protein expression of Bcl-2 significantly decreased(P<0.05),while the expression of MDM2 mRNA and MDM2,p-p38 MAPK proteins had no changes(P>0.05). Conclusion Inhibition of p38 MAPK signaling pathway inhibits the p53-mediated apoptosis pathway by promoting the expression of MDM2,thereby reducing renal cell apoptosis in rabbits with urosepsis.