Immediate hemorrhage control without secondary injury is pivotal for saving lives. In this study, polymerized glycidyl methacrylate derivative dextran/acrylic acid (poly(DEX-GMA/AAc)) microgel particles were prepared via emulsion polymerization method as a hemostatic agent. Microgel particles with size distribution of 500–800 nm were chosen because they showed more appropriate characteristics of swelling ratio and gelation time. The results revealed that the microgel particles had excellent swelling ratio of 68.95 g g−1 (w/w), which was 8.4 times that of counterpart clinically used microporous polysaccharide hemospheres, Arista. And poly(DEX-GMA/AAc) showed very short gelation time of 10–13 s. As a result, a gelled film could be formed rapidly after poly(DEX-GMA/AAc) absorbed water in blood when used on wounds, and then staunched bleeding. Poly(DEX-GMA/AAc) microgel particles showed better clotting ability than commercial hemostatic agent Flashclot in vitro. In addition, poly(DEX-GMA/AAc) did not cause exothermic burn when absorbing liquid, which was superior to Flashclot. No obvious toxicity was found in cytotoxicity study and skin irritancy test. Blood loss and hemostasis time were dramatically reduced by poly(DEX-GMA/AAc) microgel particles in hemorrhage models of ear vein, ear artery, liver and femoral artery in rabbits. These results indicated that the poly(DEX-GMA/AAc) microgel particles are a potential hemostatic agent with almost no cytotoxicity and good biocompatibility.