Objective · To explore the expression levels of miR-23a-3p and miR-27a-3p in the sera of mice with ulcerative colitis (UC) and their potential action mechanisms. Methods · Twenty C57BL/6 mice were randomly divided into the control group and the model group with 10 mice in each group. The model group mice were induced orally by water with 5% dextran sulfate sodium (DSS) for 7 d. During the induction period, the general condition, fecal morphology and occult blood status of the mice were observed. After 7 d, the whole blood and colon tissues of mice were collected, and the colon lengths and wet weights were measured. The expressions of miR-23a-3p and miR-27a-3p in the sera were detected by qRT-PCR. The expressions of peroxisome proliferator-activated receptor γ, coactivator-1α (PPARGC1A), PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2), B-cell lymphoma-2 (BCL-2), BCL-2 associated X protein (BAX), cytochrome c (CYT-C) and cleaved cysteine-containing aspartate-specific protease (cleaved-caspase-3) were detected by Western blotting. Results · After DSS induction, the model group mice showed mental depression, weight loss, diarrhea, and bloody stool, whose colon lengths were shortened and colon wet weights decreased. The UC model was constructed successfully. In the model group, the expressions of miR-23a-3p and miR-27a-3p in the sera decreased significantly (P<0.05), and the expressions of PPARGC1A, PHLPP2, BAX, CYT-C and cleaved-caspase-3 in the colon tissues increased significantly (P<0.05), but BCL-2 decreased (P<0.05). Conclusion · The expressions of miR-23a-3p and miR-27a-3p are low in the sera of UC mice, which may be involved in the occurrence and development of UC by up regulating the expressions of PPARGC1A and PHLPP2 in the colons and triggering mitochondrial pathway to induce apoptosis.