Objective To explore, by constructing a mouse fetal inflammatory response syndrome ( FIRS) model, the possible mechanism by which MMP-9/ TIMP-1 expression in premature infants with FIRS induces myocardial damage and potential drugs against this. Methods This study was divided into two parts: clinical observation and animal experiment. In part 1, a total of 118 premature infants who were in the Fourth Hospital of Hebei Medical University during the period from May 2018 to December 2019 were included as the study participants. According to whether FIRS was diagnosed, they were divided into the FIRS group (n= 61) and control group ( n= 57). The levels of IL-6, MMP-9 and TIMP-1, the MMP-9/ TIMP-1 ( M/ T) ratio, and the occurrence of myocardial injury were compared between the two groups. For part 2 ( the animal experiment), FIRS mice were constructed and divided into the following three drug intervention groups: FIRS group, RA(retinoic acid)group, and control group. Heart tissue was collected from the mice in these groups and used to detect the IL-6, MMP-9 and TIMP-1 levels and the M/ T ratio. Results The IL-6, MMP-9 and TIMP-1 levels and M/ T ratio in the FIRS group were: (38. 53±9. 01) pg / L, (42. 27±12. 53) ng / L, (110. 48±17. 06) ng / L and (38. 30±9. 93)%, respectively; these values were significantly higher (P<0. 05) than those in the non-FIRS group. The myocardial injury rate was significantly higher (P= 0. 001) in the FIRS group (27. 87%) than in the non-FIRS group (5. 26%). In the myocardial tissue of mice in the FIRS group, there were significant levels of edema, the ventricular wall became thinner, and the degree of cardiac structure changes was reduced by RA intervention. The IL-6, MMP-9 and TIMP-1 mRNA expression levels and M/ T ratios in the FIRS group at different timepoints were significantly higher than those in the control group (P<0.05), whereas the the mRNA expression of IL-6 ,MMP-9 levels and M/ T ratios in the RA group were significantly higher than those in the control group (P<0. 05) but were lower than those in the FIRS group (P<0.05). Conclusions FIRS can mediate the occurrence of heart injury in premature infants by releasing IL-6 and by regulating the levels of MMP-9 and TIMP-1 and the M/ T ratio. The application of RA can play a protective role in the process of heart injury and could be a potential drug for providing clinical treatment of FIRS.