Purpose: This study investigates the efficacy of D-4F, an apolipoprotein A-1 mimetic with antioxidant and vasodilatory properties, in preventing vibration-induced endothelial cell damage. Methods: Forty S-D rats were assigned to five groups: sham and D-4F groups with vibration for either one or three days, as well as a non-treatment, non-vibration control. Intraperitoneal injections of saline or 3 mg/kg D-4F were given one hour prior to experiment and continued for the study period. Tails received 4 h/day of vibration for one or three days. Injury was determined by light microscopy, electron microscopy, NFATc3 immunostaining, nitrated tyrosine levels, and morphometric analysis. Results: Vacuolar changes were seen at one day and loss of endothelial cells at three days of vibration; minimal damage was seen in the D-4F group. Vasoconstriction in control groups was stastically significant when compared to D-4F groups at one and three days. Stastically increased immunostaining and levels of nitrated tyrosine, markers of cell injury, were seen in contol groups when compared to D-4F. Conclusion: This study has shown that D-4F reduces early endothelial cell damage in rat tails exposed to vibration injury. This indicates that vasoprotective agents may be beneficial in the prevention of hand arm vibration syndrome.