Objective:To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) on injury of dopaminergic cells and its underlying mechanisms. Methods: CATH.a cells, a dopaminergic neuronal cell line stably expressing Ang Ⅱtype 1 receptor (AT1R) and Ang Ⅱ type 2 receptor (AT2R), were exposed to rotenone alone or in combination with Ang Ⅱ for 24 h. The cell survival rate was measured by methyl thiazolyl diphenyl-tetrazolium bromide (MTT). The protein levels of AT1R and AT2R were detected by Western blot. The intracellular levels of reactive oxygen species (ROS) were monitored using flow cytometry. The levels of gp91phox and p67phox, the two main subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, were examined by RT-PCR and immunofluorescence stainning. Results: The results showed that rotenone caused a significantly reduction on the survival rate of CATH.a cells (P < 0.05), which could be further exacerbated by Ang Ⅱ via an AT1R-dependent manner (P < 0.05). Meanwhile, we revealed that Ang Ⅱ exacerbated the rotenone-induced increase in intracellular levels of ROS (P < 0.05) as well as the expression of gp91phox and p67phox (P < 0.05). This exacerbation was abolished by NADPH oxidase inhibitor apocynin (P < 0.01) or AT1R blocker losartan (P < 0.01). Conclusion:These findings indicate that Ang Ⅱ interacts with AT1R and subsequently exacerbates the rotenone-induced injury of dopaminergic cells via elevation of ROS levels through a NADPH oxidase-dependent manner. These findings have deepened our understanding on the role of Ang Ⅱ in the pathogenesis of Parkinson’s disease, and support the use of AT1R blockers in the treatment of this devastating disease.