This study examined the extent by which changes in the concentrate level and neutral detergent fiber (NDF) content in the diet as well as the severity of acidotic insult, measured as the duration time of rumen pH below 6.0 and daily mean rumen pH, and the concentration of endotoxin in the rumen fluid are involved in the development of inflammatory conditions in cattle. A meta-analytical approach accounting for inter- and intraexperimental variation was used to generate prediction models, and data from recent studies were used to parameterize these models. A total of 10 recently conducted experiments with 43 different dietary treatments fulfilled the criteria for inclusion in this study. Diets of all of the experiments included in this meta-analysis were based on rapidly degradable grain sources, such as barley and wheat, and the findings of this study apply only to these kinds of diets. Data indicated that greater levels of concentrate in the diet were associated with increased concentrations of rumen endotoxin (R(2)=0.27), plasma haptoglobin (R(2)=0.19), and serum amyloid A (SAA) level (R(2)=0.46). Similar correlations, but in opposite directions, were observed between dietary NDF content and rumen endotoxin (R(2)=0.39) and plasma SAA concentrations (R(2)=0.22). The meta-analysis revealed that the relationships between those variables were not linear. Additionally, the breakpoint model fitted to the data of rumen endotoxin, plasma haptoglobin, and SAA indicated the presence of a threshold level of dietary concentrate and NDF, above which those responses became linear to increasing amounts of concentrate or decreasing contents of NDF in the diet. Also, feeding cattle more than 44.1% concentrate or less than 39.2% NDF in the diet was associated with a linear increase in the risk of systemic inflammation. Low daily mean rumen pH (R(2)=0.38) and duration of rumen pH <6.0 (R(2)=0.59) were associated with increased concentrations of endotoxin in the rumen fluid; although those events were not always associated with systemic inflammation. Accordingly, only 15 to 21% of the overall variation in the responses of SAA was explained by variables of rumen pH, whereas the concentrate level in the diet accounted for 46% of this variation. In conclusion, data from this study indicated the presence of thresholds of dietary concentrate and NDF levels in the diets based on rapidly fermentable grains beyond which the risk of systemic inflammation in cattle increases linearly.