Objective To determine the miRNA expression and screen key miRNA in acute stage of skin expansion. Methods Skin expansion model was established and skin samples were harvested in acute stage. Unexpanded skin was also harvested as control. miRNA microarray was undertaken to reveal the miRNA expression change during acute expansion process. T test and fold change of differential expression were applied to screen key miRNAs. TargetScan and miRDB were used to predict target genes of key miRNA. Pathway analysis was performed for target genes by KEEG and IPA. Results Eleven key miRNAs were detected which regulate pathways involve cell proliferation, differentiation, vascularization, fibrosis and tumorigenesis. Conclusion Eleven key miRNAs determined in the present study regulate important pathways in acute stage of skin expansion and they could serve as targets in skin expansion.