BACKGROUND Chlorogenic acid (CGA), a dietary polyphenol derived from many plants, has been previously reported to exert neuroprotective properties. However, its pharmacological role in Parkinson's disease (PD) and the underlying mechanisms are unclear. MATERIAL AND METHODS In the present study, we investigated the beneficial effects of CGA against the toxicity of 6-hydroxydopamine (6-OHDA) in animal and cellular models. One week after 6-OHDA administration, the behavioral activities of rats were determined by rotarod test and apomorphine-induced rotational test. The viability and apoptosis of SH-SY5Y cells following 6-OHDA exposure were determined by MTT assay and annexin V-FITC/PI double staining, respectively. The activities of antioxidant enzymes in the rat striatal tissues and SH-SY5Y cells were detected by ELISA. RESULTS The results demonstrated that 6-OHDA-induced PD-like behavioral impairments of rats were significantly forestalled by CGA administration. The increased apoptosis and reduced activities of antioxidant enzymes in the striatum of 6-OHDA-lesioned rats were also attenuated by CGA. Moreover, in an in vitro experiment, the impaired viability and enhanced apoptosis of 6-OHDA-injured SH-SY5Y cells were significantly restored by CGA pretreatment. In addition, CGA also obstructed 6-OHDA-induced ROS production and endoplasmic reticulum (ER) stress in SH-SY5Y cells. CONCLUSIONS Taken together, these data show that CGA might be an effective neuroprotective compound that mitigates oxidative stress and ER stress in PD.