AIM: To explore the miRNAs profile of CD4(+) T lymphocytes in asthma via next generation sequencing. METHODS: In the murine model of acute asthma, spleen CD4(+) T lymphocytes were sorted, in which small RNAs were extracted and sequenced. Novel miRNAs were measured with real time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: A total of 127 miRNAs were found to exhibit at least twofold change. In the 262 predicted novel miRNAs, 14 novel miRNAs were measured in qRT-PCR in the sorted CD4(+) T cells or in the differentiated Th1/Th2 cells and novel miR-11 (xxx-m0228-3p) was significantly decreased in the sorted CD4(+) T cells from the murine model of asthma and in the Th2 cells. CONCLUSION: Aberrant miRNAs profile in the CD4(+) T lymphocytes from acute asthma was documented.