The present study was carried out to evaluate the inlammatory response during acute ruminal drinking in milkfed calves and to describe the correlation between production of acute phase cytokines and the occurrence of depression in this clinical condition. For this purpose, twenty calves with acute ruminal drinking as well as ten clinically normal calves were included in the study. Blood and ruminal luid samples were collected from all examined calves. The blood samples were used to obtain a blood gas profile and for estimation of selected acute phase proteins and pro-inlammatory cytokines. A depression score was adopted to emphasize the relationship between the severity of the clinical signs and levels of acute phase cytokines. It was found that interleukin-1beta; interleukin-6, interferon gamma, c reactive protein, haptoglobin, and fibrinogen were significantly higher in diseased calves compared to the control group. There was also a positive correlation between the depression score and the examined acute phase cytokines. Our findings suggest that the acidity of the rumen Leads to inlammation of papillae with subsequent distinct inlammatory reaction. It seems that the pro-inlammatory cytokines play a role in the pathogenesis of acute ruminal drinking in milk-fed calves.