A hand-activated syringe (14) is disclosed that uses a vacuum to retract a plunger (54) of the syringe (14) to draw fluid into a syringe body (18). A first seal (76) with the plunger (54) and a second seal (64) with the plunger (54) define a vacuum chamber (82). The spacing between the first seal (76) and the second seal (64) changes in response to the plunger (54) moving relative to the syringe body (18). Advancing the plunger (54) in a direction associated with a discharge stroke creates or increases a vacuum within the vacuum chamber (82) by increasing a spacing between the first seal (76) and the second seal (64). This vacuum thereafter may be used to retract the plunger (54) by decreasing a spacing between the first seal (76) and the second seal (64), and to thereby draw fluid into the syringe (14) from a fluid source (86).