Purpose: To characterize the real-time intraocular pressure (IOP) and ocular pulse amplitude (OPA) responses to controlled increases in intracranial pressure (ICP) and mean arterial blood pressure (MAP). Methods: Simultaneous recordings of the intraocular, intracranial and arterial pressure changes were performed in urethane anesthetized Sprague-Dawley rats. Pressure changes were measured using solid-state micro-sensor catheters (Scisense) inserted into each compartment. Controlled elevations in ICP and MAP were simulated by a cranial ventricular saline infusion (20 μl / minute over 10 minutes) and an intravenous vasopressor agent (phenylephrine 50 μg / kg / min over 2 minutes) respectively. Results: Simulations of transient systemic hypertension (MAP increase of 31 ± 6.3 mm Hg, n = 9) resulted in instantaneous increases in both IOP and ICP. (1.3 ± 0.4 mm Hg and 3.7 ± 0.8 mm Hg respectively, P < 0.05). Using our intracranial ventricular saline infusion protocol, a maximal increase in ICP from baseline of 9 ± 1.2 mm Hg (n = 7) was achieved. The increase in ICP was accompanied by a trend increase in IOP (0.4 ± 0.2 mm Hg, although it did not reach statistical significance (P = 0.07). There was no significance change in the OPA measured during baseline and during the ICP or MAP challenge. Conclusion: IOP is influenced by short-term physiological fluctuations in MAP and to a lesser extent by fluctuations in ICP. Further research is required to evaluate whether chronic elevations in MAP and ICP may have clinically significant influences on IOP and OPA.