Duck plague (DP) or duck viral enteritis is a fatal viral disease of ducks that causes huge economic losses in the duck industry. The present study was performed to determine the immune response and protective efficacy of an inactivated DP vaccine prepared from a local virulent DP virus. A virulent DP virus was obtained from the laboratory repository of the Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh (Bangladesh). The DP virus (EID50 105.3/ml) was inactivated using 0.04% formalin. The alum (40 g/L) was added to the inactivated DP virus as an adjuvant. A total of 60 Khaki Campbell male ducks aged 17 weeks were randomly divided into three groups. Ducks of groups A (n = 20) and B (n = 20) were vaccinated intramuscularly in the breast muscle with 1 ml of inactivated DP vaccine and a live attenuated DP vaccine, respectively. Ducks of group C (n = 20) were kept as unvaccinated control. Booster vaccination was administered at 2 weeks after primary vaccination. Antibody titers of vaccinated ducks were measured at 7, 14, 21, and 28 days post-vaccination (DPV) using a passive haemagglutination (PHA) test. Ducks of both vaccinated and unvaccinated groups were challenged with 1 ml virulent DP virus (EID50 104.3/ml) at 28 DPV. Clinical signs, morbidity and mortality, and gross pathological lesions of vaccinated and control ducks were observed for 10 days post-challenge to evaluate the protective efficacy of inactivated DP vaccine. The mean PHA antibody titers of vaccinated ducks of group A at 7, 14, 21, and 28 DPV were 5 ± 0.43, 26 ± 1.71, 43 ± 3.4, and 54 ± 3.28, respectively. Ducks in group B had mean serum PHA antibody titers of 21 ± 1.71, 41 ± 3.28, 52 ± 3.41, and 84 ± 7.25 at 7, 14, 21, and 28 DPV, respectively. No mortality or gross pathological lesions were observed in vaccinated ducks after they were subjected to a challenge infection. Additionally, no significant difference was observed between groups A and B in terms of the challenge infection. The mortality rate of the control group of ducks was 70%. Hemorrhage in the trachea and intestine and necrotic foci in the liver were seen in unvaccinated control ducks (group C). Experimentally developed inactivated DP vaccine induced a protective serum antibody titer and conferred 100% protection against virulent challenge infection up to 10 days observation period.