Abstract: This study investigated the effects of dietary Se levels on lipid metabolism and miRNA expression in the mesenteric adipose tissue of yellow catfish. Three experimental diets were formulated to contain 0.03 (low Se), 0.25 (adequate Se, control) and 6.39 mg Se/kg (high Se) for a 12-week trial. The enzymatic activities of lipogenesis, the expression levels of miRNA and its target gene related to lipid metabolism were detected. Compared with the control group, TG content increased significantly in the high-selenium group and low selenium group (P<0.05). Compared with the control group, the enzyme activities of G6PD and 6PGD decreased significantly in the low Se group (P<0.05), and significantly increased in the high Se group (P<0.05). Compared with the control group, the enzyme activity of ICDH decreased significantly in the high-Se group (P<0.05) with no significant change in the low-Se group; the enzyme activities of ME and FAS both increased significantly in the low and high Se groups (P<0.05); the expression levels of mir-26a, mir-183, mir-135, let-7b, let-7c and let-7g in the high Se group increased significantly (P<0.05) with no significant difference in the low Se group. Though mir-181a-5p and let-7e increased significantly in the low-selenium group (P<0.05), it showed no significant difference in the high-selenium group. Selenium significantly increased mir-130 and mir-203a (P<0.05). Low selenium decreased significantly but high selenium increased the expressions of miR-200a, miR-143, let-7d and let-7f (P<0.05). MiR-143, miR-203a and miR-130 were highly expressed in adipose tissue, which were strongly responded to dietary Se levels. We used TargetScanFish6.2 and miRwalk3.0 to predict target genes of miR-130, miR-203a and miR-143, and performed KEGG enrichment analysis of target genes. The target genes of miR-143 enriched significantly in mineral absorption, unsaturated fatty acid biosynthesis and insulin pathway (P<0.05, FDR≤ 0.05). The target genes of miR-203a was significantly enriched in lipid metabolic pathways and insulin signaling pathways (P<0.05, FDR≤0.05). The target genes of miR-130 enriched significantly in sphingolipid metabolism, lipid accumulation and mTOR signaling pathway (P<0.05, FDR≤0.05). Comprehensive analysis found that miR-130, miR-143 and miR-203a target genes were enriched in fatty acid synthesis signaling pathway, autophagy, apoptosis and insulin resistance. Then we selected target genes that both enriched in these signaling pathways for qPCR. The fas, cpt1a, hsl, srebp1, pparα and atgl mRNA expressions was consistent with miR-143, miR-203a and miR-130 expression levels. Therefore, we speculated that the dietary Se induced lipid metabolism via miR-143-, miR-203a- and miR-130-mediated expressions of fas, cpt1a, hsl, srebp1, pparα and atgl.