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We recently reported that priming donor lungs with thioredoxin-1 (Trx) prolongs allograft survival associated with inhibition of host spleen T cell response to donor antigen and cytokine modulation in a rat model of lung transplantation. The molecular events associated with Trx primed allograft survival and modulation of spleen T cell responses remained to be determined. Since micro-RNAs (miRNAs) play a critical role in the regulation of physiological and immunological responses via modulation of target gene and protein expression, we examined the impact of Trx-priming of donor lungs on miRNA expression profile of spleen CD4⁺T cells isolated from transplanted rats. Donor lungs were primed with Trx for 4 h prior to transplantation. Four days post transplantation recipient spleen CD4⁺T cells were isolated to identify miRNA profile by microarray analysis using 498 detectable rat miRNAs. Expression of the six mRNA (miR-342-3p, miR-128, miR-30b, miR-92a, miR-25, miR-146a) were significantly up-regulated whereas twelve miRNA (mir-301b, miR-33, miR-210, miR-206, miR-494, miR-29b, miR-196c, miR-362, miR-466b-2, miR-758, miR-466c, miR-101a) were significantly down-regulated in Trx-primed donor lung recipient’s spleen CD4+T cells. These sets of miRNAs are associated with modulation of multiple pathways that appeared to play critical role in the regulation of inflammatory responses and T cell proliferation after transplant injury and allograft dysfunction. The impact of Trx-priming on selective miRNA expression with protective role may provide novel therapeutic strategy to limit or prevent injury and promote allograft survival.