Background: The present study has been designed to compare the effect of magnesium sulfate with mannitol on reducing intraocular pressure (IOP). Materials and Methods: During the phacoemulsification surgery, 105 patients randomly divided into three groups receiving 20% mannitol at a dose of 0.3 g/kg, 50% magnesium sulfate at a dose of 20 mg/kg, and placebo (normal saline), with the same volume (100 ml) and infusion time (10 min), were used for the first, second, and third groups, respectively. The IOP was measured before and immediately after the injection and 5 min after the end of the surgery and compared between the groups. Results: The mean IOP immediately after the injection had a significant difference in three groups (mannitol: 15.2 ± 2.5, magnesium sulfate: 14.7 ± 1.9, and normal saline: 13.8 ± 2.8; P = 0.044), and the IOP had a significant difference between normal saline and mannitol groups (0.027) while there was no significant difference between mannitol and magnesium sulfate groups (P = 0.34) and also between magnesium sulfate and normal saline groups (P = 0.2). Conclusion: Using magnesium sulfate had no effect on changes in the IOP and hemodynamic of patients during the surgery. Using mannitol may be effective in reducing IOP while no effect of magnesium sulfate on IOP was found.