Peroxisome proliferator-activated receptors 灌 (PPAR灌) is known to be expressed ubiquitously, and is a predominant PPAR subtype of cardiac cells. However, relatively less is known about the role of PPAR灌 in cardiac cells except that PPAR灌 ligand treatment protects cardiac hypertrophy by inhibiting NF-觀B activation. Thus, in the present study, we examined the effect of selective PPAR灌 ligand L-165041 on angiotensin II (AngII) induced cardiac hypertrophy using cardiomyocyte and its underlying mechanism. According to our data, in cultured cardiomyocytes, L-165041 (10關M) inhibited AngII-induced [3H] leucine incorporation, induction of the fetal gene atrial natriuretic factor (ANF) and increase of cardiac myocyte size. L-165041 also prevented the AngII-induced reduction in the expression of genes involved in fatty acid oxidation such as pyruvate dehydrogenase kinase 4, muscle type carnitine palmitoyltransferase. Activation of focal adhesion kinase (FAK) is implicated in the progress of cardiomyocyte hypertrophy and L-165041 pretreatment significantly inhibited AngII-induced phosphorylation of FAK. FAK phosphorylation by AngII was inhibited by intracellular Ca2+ chelator BAPTA-AM pretreatment, and L-165041 abrogated the increase in intracellular Ca2+ level by AngII suggesting involvement of Ca2+ signaling pathway in PPAR灌 effect. Phosphorylation of FAK is required for downstream signaling to MAPK cascades. AngII-induced ERK activation is inhibited by L-165041 and BAPTA-AM pretreatment in cultured cardiomyocytes. Overexpression of PPAR灌 using adenovirus significantly inhibited AngII-activated FAK expression and intracellular Ca2+ increase. In conclusion, our data indicate that PPAR灌 inhibits AngII induced cardiac hypertrophy possibly by suppressing intracellular Ca2+ signaling pathway.