Purpose. The goal of this study was to determine if systemic calcium channel blockade in the mouse model of oxygen induced retinopathy during the period of vascular injury (hyperoxia) would modulate the resultant retinopathy. Methods. C57BL6 mice pups were placed in 75% oxygen from postnatal day 7 through 12 (Smith et. al., IVOS, 1994) to induce retinal neovascularization which is maximal at postnatal day 17-21. Mice pups received varying doses of diltiazem (0.05, 0.2, and 0.5 mg/kg/day) from day 7 to 12. Animals were sacrificed at day 17-21 and retinal neovascularization was assessed by quantification of extra retinal neovascular nuclei in retinal sections and by a retinal scoring system of whole mount preparations. Results. Animals who received 0.2 and 0.5 mg/kg/day of diltiazem concurrent with oxygen exposure had significantly lower degrees of retinopathy as assessed by the neovascular nuclei and the retinal scoring system (p<0.01). Animals who received 0.05 mg/kg/day of diltiazem concurrent with oxygen exposure had similar retinopathy when compared to animals receiving oxygen alone. Control animals who were not exposed to oxygen showed no differences in retinal evaluation when compared to animals receiving the various doses of diltiazem. Animal growth was equal across the groups. Conclusions. Diltiazem improves oxygen induced retinopathy in the mouse in a dose dependent fashion and does not affect normal retinal vascularization. We speculate that diltiazem modulates retinal vasoconstriction or vascular injury early in the mouse model, thus improving the resultant retinopathy.