The aim of this study was to evaluate the effect of tulathromycin as a bovine respiratory disease (BRD) metaphylactic treatment on rumen fluid parameters in feedlot cattle in an intensive livestock production farm. One hundred beef cattle, immediately after housing, were divided in 2 equal groups: 50 animals with metaphylactic treatment against BRD (treated group; tulathromycin at 2.5 mg/kg BW) and 50 animals with placebo treatment (control group). Rumen fluid samples were collected from each animal by rumenocentesis in 3 periods: 1 d (T1), 8 d (T8), and 15 d (T15) after treatment. Rumen pH was determined by ruminal fluid using portable pH meter. Total volatile fatty acids (total VFA) were evaluated by high performance liquid chromatography (HPLC). All animals were singularly weighed at T1 and T15. Two-way analysis of variance (ANOVA) was applied to determine significant effects of treatment (treated group versus control group) and period (T1, T8, and T15) on rumen fluid parameters and body weight. No clinical signs of BRD or other related diseases were recorded during the periods of study from any animal. Statistically significant differences (P < 0.05) were found between treated group and control group for mean values of ruminal pH (6.02 versus 5.89) and total VFA (5.84 versus 5.13) at 8 d after treatment. The weight gain (Δ) showed an average increase of 8.6 kg in treated group (P < 0.05). The trends of ruminal pH and VFA values suggest an effect of tulathromycin as BRD metaphylactic treatment on the modulation of rumen fermentation, particularly 8 d after administration.