Rosmarinic acid (RA) is a naturally occurring polyphenolic compound. It is found in several herbs in the Lamiaceae family, such as Perilla frutescens. RA has been reported to exert anti-oxidative effects on rat erythrocyte, liver, and kidney cells. However, little is known about the effects of RA on dopaminergic cells. In the present study, we investigated whether RA could protect MES23.5 dopaminergic cells from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. The results showed that RA pretreatment significantly prevented 6-OHDA-induced cell viability reduction. Further experiments demonstrated that 6-OHDA induced intracellular reactive oxygen species generation and decreased the mitochondria membrane potential (DeltaPsim). These effects could be partially reversed by RA pretreatment. However, RA had no direct chemical reaction with 6-OHDA extracellularly in a cell-free system. Taken together, these results suggest that RA could exert its protective effects against 6-OHDA-induced neurotoxicity through its anti-oxidation properties. Thus, we propose that RA should be viewed as a potential chemotherapeutic in Parkinson's disease patients.