Transition to grain increases inflammation and causes parakeratosis, which can decrease growth performance in fattening animals. It is unknown if ruminants adapt to these inflammatory responses over time. In a three-phase, 49-day experiment, all wethers (n = 13, BW = 50.6 ± 4.7 kg; 4.9 ± 0.3 months of age) were fed an 80% forage diet during P1(day 0 to 21). On day 21, 4 wethers were slaughtered to obtain baseline liver and rumen tissue. During P2 (day 22 to 25), the remaining wethers were fed an 80% concentrate diet. Four wethers were slaughtered on day 25 to obtain P2 liver and rumen tissue. During P3 (day 22 to 49), the remaining five wethers were fed 80% concentrate diets and were slaughtered on day 49 to obtain P3 liver and rumen tissue. Rumen parakeratosis was greater (p ≤ 0.02) in wethers sampled in P2 and P3 when compared to those sampled in P1. Among positive acute phase reactants, expression of serum α-amyloid (SAA) and haptoglobin (HPT) tended (p ≤ 0.12) to be 6- and 10-fold greater, respectively, in wethers sampled in P2 compared to wethers sampled in P1; however, SAA and HPT expression was not different between wethers sampled in P3 and P1. Plasma glucose and β-hydroxybutyric acid (BHBA) increased (p ≤ 0.03) in wethers sampled in both P2 and P3 compared to the wethers sampled in P1, while total protein and cholesterol decreased (p ≤ 0.06) only in wethers sampled from P2 compared to those sampled in P1. Hepatic acute phase responses suggest that the wethers adapted to an 80% concentrate diet over time.