Angiopoietin-like 4 (ANGPTL4) is a potent regulator of triacylglycerol metabolism but knowledge of the mechanisms underlying ANGPTL4 transcription in response to fatty acids is still limited in teleost. In this study, we explored the molecular characterization of ANGPTL4 and regulatory mechanisms of ANGPTL4 in response to fatty acids in large yellow croaker (Larimichthys crocea). Here, croaker angptl4 contained a 1416 bp open reading frame encoding a protein of 471 amino acids with highly conserved 12-amino acid consensus motif. Angptl4 was widely expressed in croaker, with the highest expression in the liver. In vitro, oleic and palmitic acids (OA and PA) treatments strongly increased angptl4 mRNA expression in croaker hepatocytes. Moreover, angptl4 expression was positively regulated by peroxisome proliferator-activated receptor family (PPAR-α, β and γ) and expression of pparγ was also significantly increased in response to OA and PA. Moreover, inhibition of PPARγ abrogated OA or PA-induced angptl4 mRNA expression. Beyond that, PA might increase angptl4 expression partly via the insulin signaling. Overall, the expression of ANGPTL4 is strongly upregulated by OA and PA via PPARγ in the liver of croaker, which contributes to improve the understanding of the regulatory mechanisms of ANGPTL4 in fish.