The effects of sesamin on dopamine biosynthesis in PC12 cells were investigated. Sesamin at concentration ranges of 20-75 ${mu}M$ significantly increased intracellular dopamine levels and tyrosine hydroxylase (TH) activities at 24 h: 50 ${mu}M$ sesamin increased dopamine levels to 132% and TH activities to 128% of control levels. Sesamin (50 ${mu}M$) induced the phosphorylation of TH, cyclic AMP-dependent protein kinase (PKA) and cyclic AMP-response element binding protein (CREB) for 0.5-24 h. Sesamin (50 ${mu}M$) also increased the mRNA levels of TH and CREB for 3-24 h. In addition, sesamin (50 ${mu}M$) associated with L-DOPA (50 and 100 ${mu}M$) further increased the intracellular levels of dopamine for 24 h compared to L-DOPA alone. These results suggest that sesamin enhances dopamine biosynthesis and L-DOPA-induced increase in dopamine levels by inducing TH activity and TH gene expression, which is mediated by PKA-CREB systems in PC12 cells. Therefore, sesamin could serve as an adjuvant phytonutrient for neurodegenerative diseases.