Yersinia enterocolitica is a bacterial pathogenic organism which distributed widely in several countries including Iraq, among a broad range of environmental and animal reservoirs as cattle. In last decades, this bacterium has gained an increasing attention due to its role as an emerging foodborne pathogen within the context of globalized food supply chains and antimicrobial resistance. Hence, this stud aims to isolate Y. enterocolitica from the diarrheic cattle, preparation of bacterial ghosts (BGs) from this bacterium and experimental evaluation its efficiency in stimulating immune response in mice. Initially, fresh feces were obtained from 87 diarrheic cattle at Al-Diwaniyah city (Al-Qadisiya, Iraq) during November (2023)-May (2024), and processed to isolate Y. enterocolitica strain that used to preparation stocks of Y. enterocolitica ghosts (YEGs). Then, a total of 30 mice were selected and divided into NCG (not injected YEGs), SCG (mice injected an adjuvant YEGs (70μg/100μl), subcutaneously), and IMG (mice injected an adjuvant YEGs (70μg/100μl), intramuscularly). The mice were injected once at 0, 2, 4 and 8 weeks of study experiments. Then, blood samples were drained from all study mice to pipette sera for serologicy using ELISA to measurement the levels of serum IL-1, IL-2, and IFN-. Our findings revealed that 16.09% of study cattle were positively infected by In Y. enterocolitica. Experimentally, the findings of IL-1 were shown a significant reduction in values of SCG (11.99±2.38pg/ml) but insignificant variation (p>0.05) in values of IMG (59.74±12.2pg/ml) in comparison to values of NCG (61.68±12.38pg/ml). Concerning IL-2, values of experimental groups, SCG (8.98±1.24pg/mL) and IMG (8.11±1.44pg/mL) were obviously greater than NCG (2.92±0.32pg/mL). Significant elevation of IFN- was recorded in experimental groups, SCG (282.61±28.3pg/mL) and IMG (370.24±20.5pg/mL), when compared to values of NCG (104.30±25.4pg/mL). Among experimentally groups, values of IMG were much more than SCG.This study indicated the robust adjuvant properties of YEGs as a vaccine in inducing of immune response and enhancing of immunogenicity, making them potent stimulators of both innate and adaptive immune responses.