Objective：To determine the pathological significance of serum miR-21 expression level in premature respiratory distress syndrome（RDS）infants. Methods：Randomized blood samples were collected from RDS and non-RDS infants in the Neonatal Intensive Care Unit（NICU）of Jiangsu Province Hospital from June to December 2015. Total RNA was extracted from each blood sample and reverse transcribed into complementary DNA（cDNA）. We used real-time reverse transcription polymerase chain reaction（RT-PCR）technique to determine the serum miR-21 expression levels in the RDS and the non-RDS groups（n=30 and n=21，respectively）. Unpaired student t-test was used to compare the significance between groups. Results：The serum miR-21 expression level in the RDS group was significantly higher than that in the control group（P < 0.05）. The miR-21 expression levels in the moderate to severe RDS groups appeared to be higher than that in the mild groups，however，statistic significance was not reached in our study. In addition，the RDS group that received pulmonary surfactant therapy had significant increase in miR-21 expression levels（P < 0.05）. Conclusion：Serum miR-21 expression level is closely related to the development of infant RDS，suggesting that miR-21 is involved in the pathogenesis of infant RDS.