Technical Abstract: Acute phase proteins (APP) are serum proteins elevated in response to a variety of physiological injuries including infection and inflammation. These pathogen nonspecific proteins are predominantly synthesized in the liver and serve as a humoral component of innate immunity by way of recognizing and neutralizing pathogens, and facilitating tissue repair. The nature of APP and their physiological significance is not understood in sub mammalian species. In studying the avian acute phase response in experimental inflammation induced by endotoxin or croton oil, we identified serum transferrin as a major avian APP that was same as the ovotransferrin (OVT) present in the egg white. Using an enzyme-immunoassay, the results showed the serum OVT to be elevated during a variety of bacterial and viral infections. The ability of OVT to modulate avian macrophage and heterophil functions was evaluated using in vitro assays. The results showed that OVT activated both of these cell types as measured by nitric oxide, interleukin-6, matrix metalloproteinase, and reactive oxygen production. Additionally, OVT also stimulated heterophil degranulation. These results demonstrate that beyond its antibacterial effects, the OVT may act as a natural immunomodulator enhancing innate immune function.