Disclosed is a fusion protein Slit2D2-HSA formed by fusion of a Slit2D2 polypeptide and a human serum albumin HSA, and use thereof for the manufacture of a medicament for prophylaxis and/or treatment of sepsis, and the said fusion protein Slit2D2-HSA retains the pharmacological activities of Slit2 in inhibition of neutrophil migration and treatment of sepsis, and has an improved stability, prolonged half-life and improved therapeutic effect of sepsis. Compared with protein of Slit2, the polypeptide of Slit2D2 has a smaller molecular weight which is much easier to be purified and separated in preparation and used in the development of drugs.