The retinal pigment epithelium (RPE) is a specialized epithelium lying in the interface between the retina and the choriocapillaris, where it forms the blood-retinal barrier. Among the main functions are the transport of nutrients, ions, and water, phagocytosis, protection against photoxidation and port of information between the blood and the retina. Recent studies indicate the existence of an intraocular renin-angiotensin system (RAS). Interestingly, modulation of systemic RAS changes neuronal activity of the retina. Besides, RPE cells express renin and angiotensin II receptor (ATR). This work aims to elucidate the molecular mechanism by which the systemic Ang II regulates the intraocular RAS. Quantitative PCR shows a decreased renin expression in the eye from ATRAP+/+ and ATRAP-/- mice treated systemically with Ang II. By RT-PCR we found that the mouse RPE expresses both AT1R and ATRAP which localize on the basolateral membrane of the RPE as shown by immunostaining. Using calcium imaging in mouse or pig RPE cells, we found that Ang II evokes Ca²⁺ response, which were partially blocked by Xestospongin C and U-73122, specific blockers of IP3R and PLC respectively. Similarly, removal of extracellular Ca²⁺ as well as perfusing SKF96365, a TRPV2 channel blocker significantly reduced the Ang II-evoked Ca²⁺ response in RPE. Taken together, these results suggest that the intraocular RAS is modulated by systemic RAS via activation of AT1R and concomitant calcium mobilization through activation of PLC, IP3 and TRPV2 channel pathways.