The present study aimed to investigate the effectiveness of a national animal disease laboratory (NADL) strain as cytopathic bovine viral diarrhea virus (cp- BVDV) infection on DNA integrity of blood derived buffalo macrophages (M) and Interferon-Gamma (IFN-γ)release in vitro. The virus (10^6.4 TCID₅₀) infect the matured M, cells in one column of inoculated M  as well as non infected M  were scraped daily and collected for DNA damage using Comet assay. The level of IFN-γ was determined too. Comet microphotograph of inoculated M along the 4 days tested period showed, balloon shaped tail with different percent of DNA damage. The DNA damage is beginning at 24 h postinoculation (PI) and reached to the maximum at 72-96 h PI as compared to the negative control. A qualitative measurement of IFN-γ in the supernatant of inoculated M as compared with the negative control revealed gradually increased of IFN-γ secretion through out tested period that beginning at the 2^nd day PI and reach to the plateau out through the 3^rd and 4^th day PI. In conclusion, BVDV has suppressive effects on immune cellsas demonstrated in vitro that damage of macrophage.