We previously reported that angiotensin II (Ang II) increases adipocyte fatty acid synthesis and triglyceride content. Triglyceride stores or adiposity correlate positively with the amount of circulating leptin. Ang II was proposed to increase adipocyte differentiation and growth by promoting prostaglandin (PG) production. The purpose of this study was to determine whether Ang II increases leptin secretion via a PG-dependent mechanism. Physiologic doses of Ang II significantly increased leptin secretion by 3T3-L1 adipocytes and human adipocytes. Elevation of PG secretions was elicited at physiologic concentrations of Ang II (P < 0.05). Secretions of 6-keto PGF(1alpha), a stable derivative of PGI(2), and PGE(2) were induced by physiologic concentrations of Ang II in a time-responsive fashion (P < 0.05). Inhibition of PG synthesis by indomethacin and aspirin significantly suppressed basal as well as Ang II-induced PG levels, but did not significantly affect basal and Ang II-induced leptin secretion. In conclusion, although Ang II stimulates both leptin and PG secretion by adipocytes, regulation of leptin secretion by Ang II in adipocytes is not mediated by a PG-dependent mechanism.