S-allyl-L-cysteine (SAC) is a sulfur-containing amino acid contained in garlic. Recent studies have demonstrated that the pharmacological effect of SAC is not only as an antioxidant effect, but also as a cell proliferation effect. In a previous study, we demonstrated that the hepatocyte proliferating effect of SAC was via the IGF-I receptor tyrosine kinase / ERK2 pathway. In addition, the SAC-stimulated hepatocyte proliferation was suppressed by somatostatin, which inhibits the secretion of autocrine factors such as IGF-I. The aim of this study is to further investigate the mechanism of SAC-induced IGF-I secretion in primary cultures of adult rat hepatocytes. The amount of IGF-I secreted from hepatocytes was quantified by ELISA. As a result, SAC significantly increased secretion of IGF-I from cultured hepatocytes at 20 min. The SAC-induced IGF-I secretion was completely suppressed by a JAK2 inhibitor TG101209, a phospholipase C Inhibitor U-73122, and an intracellular Ca²⁺ chelating agent BAPTA-AM. Moreover, phosphorylation of JAK2 was increased rapidly in SAC-stimulated hepatocytes, and the effect was suppressed by TG101209. These results suggest that SAC stimulates JAK2, subsequently activates PLC, which increases membrane phosphatidylinositol turnover and intracellular Ca²⁺ levels, resulting in autocrine IGF-I secretion.