Objective Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an important hepatic manifestation of metabolic syndrome. Sterol regulatory binding protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the liver. Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1). Cilostazol is an antiplatelet agent that prevents atherosclerosis and decreases serum triglyceride levels. However, little is known about the effects of cilostazol on hepatic lipogenesis. Here, we examined the role of cilostazol in the regulation of SREBP-1c transcription in the liver. Methods The effects of cilostazol on insulin-induced and LXR agonist (T0901317)-induced expression of SREBP-1c and its targets genes were examined by performing real time RT-PCR and western blot analysis on cultured liver cells. To investigate the effect of cilostazol on SREBP-1c at the transcription level, we performed the transient transfection reporter assay and the electrophoretic mobility shift assay (EMSA). Results Cilostazol inhibited insulin-induced and T0901317-induced expression of SREBP-1c and its downstream targets, acetyl-CoA carboxylase and fatty acid synthase, in cultured hepatocytes. Cilostazol also inhibited activation of the SREBP-1c promoter by insulin, an T0901317, and Sp1 in a luciferase reporter assay. EMSA analyses showed that cilostazol inhibits SREBP-1c expression by repressing binding of LXR and Sp1 to the promoter region. Conclusion The results indicate that cilostazol inhibits insulin-induced hepatic SREBP-1c expression via inhibition of LXR and Sp1 activity and suggests that cilostazol is a negative regulator of hepatic lipogenesis.