BACKGROUND Higher intraocular pressure (IOP) is a major risk factor for developing glaucoma, and the leading cause of irreversible blindness worldwide. High altitude (HA) may be involved in IOP, but the reported results were conflicting. Ascent to HA directly by plane from low altitude regions is an acute, effortless exposure. However, the effects of such exposure to different altitudes on IOP have rarely been reported. AIM To investigate changes in IOP after rapid effortless exposure to HA in stages and compare it with systemic parameters. METHODS Fifty-eight healthy subjects (116 eyes) were divided into three groups: 17 low-altitude (LA) residents [44 m above sea level (ASL)], 22 HA residents (2261 m ASL) and 19 very HA (VHA) residents (3750 m ASL). The LA group flew to HA first. Three days later, they flew with the HA group to VHA where both groups stayed for 2 d. Then, the LA group flew back to HA and stayed for 1 d before flying back to 44 m. IOP, oxygen saturation (SpO(2)) and pulse rate were measured. The linear mixed model was used to compare repeated measurements. RESULTS IOP in the LA group significantly decreased from 18.41 +/- 2.40 mmHg at 44 m to 13.60 +/- 3.68 mmHg at 2261 m ASL (P < 0.001), and then to 11.85 +/- 2.48 mmHg at 3750 m ASL (P = 0.036 compared to IOP at 2261 m ASL) and partially recovered to 13.47 +/- 2.57 mmHg upon return to 44 m. IOP in the LA group at HA and VHA was comparable to that in the local residents (12.2 +/- 2.4 mmHg for HA,11.5 +/- 1.8 mmHg for VHA). IOP was positively associated with SpO(2) while negatively associated with pulse rate. CONCLUSION IOP in the LA group gradually reduced as altitude elevated in stages and became comparable to IOP in local residents. Hypoxia may be associated with IOP, which deserves further study.