Objective To investigate the effect of rapamycin on cardiac damage in remote organs after renal ischemia reperfusion (RIR) in rats. Methods A total of 40 rats were randomly divided into four groups: blank group, sham operation group, RIR group and rapamycin treatment group, with 10 rats in each group. Rats in the rapamycin treatment group received gastric administration of rapamycin. Each group of rats was sacrificed 24 hours after surgery, and blood, spleen tissue and heart tissue were collected. The creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured. Semi-quantitative analysis with PAS staining indicated pathological damage to the heart. A TUNEL kit was used to detect apoptosis. The percentage of NKT cells was measured by flow cytometry. The expression levels of CXC chemokine ligand 10 (CXCL10), hypoxia-inducible factoR-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected by RT-qPCR. Results The BUN and SCr levels were higher in the RIR group than in the sham group. The serum CK and CK-MB levels were lower in the rapamycin treatment group than in the model group. Semi-quantitative scoring of cardiac pathological lesions showed that the pathological damage score of the rapamycin treatment group was significantly lower than that of the RIR group. The percentage of NKT cells in the heart and peripheral blood was significantly higher in the rapamycin treatment group than in the RIR group. The percentage of spleen NKT cells was lower in the rapamycin treatment group than in the RIR group. The expression of HIF-1α mRNA and VEGF mRNA was lower in the rapamycin treatment group than in the RIR group. The expression level of CXCL10 mRNA was higher in the rapamycin treatment group than in the RIR group. Conclusions Rapamycin can significantly up-regulate the expression level of CXCL10 and promote the migration of NKT cells from the spleen to peripheral blood and the heart. Rapamycin also inhibits HIF-1α expression levels and protects the heart after RIR.