Abstract： Objective To investigate the protective effect of progesterone (PROG) on rhabdomyolysis(RM)?induced acute kidney injury(AKI)in rats and its mechanism. Methods Forty SD rats were randomly divided into 5 groups(n=8 each),including the normal control group,model group, DMSO solvent control group,PROG intervention group and Mifepristone(Mife)group. At 24 h after venous blood samples were collected,the contents of blood urea nitrogen (BUN),serum creatinine (SCr) and creatine kinase(CK)were determined. The HE staining was used to evaluate the renal tissues. Acute tubular necrosis (ATN) semi?quantitative scoring was examined under optical microscope. Immunohistochemistry was used to determine the TNF?α and Caspase?3 protein expression of the renal tissues. Renal tubular epithelial cell apoptosis was assessed by TUNEL. Results Compared with the normal control group,the levels of CK,SCr and BUN were significantly increased (all P<0.05);serious pathological injuries were found in the renal tubular and renal interstitium with significantly increased ATN injury score(P<0.05);the TNF?α and Caspase?3 protein expression were significantly increased (P<0.05);the AOD value was significantly increased(P<0.05);and the difference of Tunel apoptosis index was statistically significant(P<0.05) in the model group. Compared with the model group,the levels of serum SCr and BUN were significantly decreased (P<0.05);there was no statistically significant difference in CK (P>0.05);the pathological injuries of renal tissues were reduced and the ATN injury score was significantly decreased(P<0.05);the TNF?αand Caspase?3 protein expression were decreased(P<0.05),and the AOD value was significantly decreased (all P<0.05);and the difference of Tunel apoptosis index was statistically significant (P<0.05) in the PROG intervention group. Conclusion PROG binding to its receptor can significantly protect glycerol?induced AKI. Its mechanism may be associated with reduced infiltration of inflammatory cells,inhibited expression of inflammatory cytokine TNF?αand decreased expression of Caspase?3 apoptosis protein in renal tissues.